Periplogenin inhibits pathologic synovial proliferation and infiltration in rheumatoid arthritis by regulating the JAK2/3-STAT3 pathway.

Rheumatoid arthritis (RA) is an autoimmune disease that affects joints, causing inflammation, synovitis, and erosion of cartilage and bone. Periplogenin is an active ingredient in the anti-rheumatic and anti-inflammatory herb, cortex periplocae. We conducted a study using a CIA model and an in vitro model of fibroblast-like synoviocytes (FLS) induced by Tumor Necrosis Factor-alpha (TNF-α) stimulation. We evaluated cell activity, proliferation, and migration using the CCK8 test, EDU kit, and transwell assays, as well as network pharmacokinetic analysis of periplogenin targets and RA-related effects. Furthermore, we measured inflammatory factors and matrix metalloproteinases (MMPs) expression using ELISA and qRT-PCR assays. We also evaluated joint destruction using HE and Safranin O-Fast Green Staining and examined the changes in the JAK2/3-STAT3 pathway using western blot. The results indicated that periplogenin can effectively inhibit the secretion of inflammatory factors, suppress the JAK2/3-STAT3 pathway, and impede the proliferation and migration of RA FLS. Thus, periplogenin alleviated the Synovial inflammatory infiltration of RA.

Antibiofilm potential of luteolin against multidrug-resistant Staphylococcus aureus isolated from dairy goats and farm environments.

Staphylococcus aureus (S. aureus) is a prominent pathogen responsible for mastitis in dairy goats, and capable of contaminating farm environments. Luteolin is a naturally derived flavonoid found in many plant types. To our best of knowledge, this study involved the initial investigation into the prevalence of S. aureus and screened the multidrug-resistant (MDR) S. aureus from raw milk samples and farm environments. Furthermore, we explored the antimicrobial and antibiofilm activities of luteolin against MDR S. aureus. Antibiofilm activity was evaluated via crystal violet staining and confocal laser scanning microscopy (CLSM). Bacterial morphology and biofilm microstructure were observed via scanning electron microscopy (SEM), and the antibiofilm mechanisms were further explored based on extracellular polymeric substance (EPS) production, extracellular DNA (eDNA) content, and quantitative reverse transcription PCR (qRT-PCR). In total, 28 and 43 S. aureus isolates were isolated from raw milk and environmental samples, respectively. Raw milk samples had the highest prevalence of S. aureus (58.33%), followed by sewage sludge (35.42%), soil (27.78%), excrement (19.44%), bulk tank (12.50%), milking parlor (11.11%), and feed (7.50%). Among the isolated strains, 40 isolates (56.34%) expressed the MDR phenotype. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of luteolin against MDR S. aureus were 8-32 µg/mL and 16-64 µg/mL, respectively. Compared to that in the untreated control isolate, the number of dead cells increased, while the auto-aggregation and cell surface hydrophobicity decreased. Moreover, the cell membrane dissolved with the increase in luteolin concentration. Luteolin down-regulated the transcription of seven biofilm related genes: icaA, icaD, icab, hld, hla, agrA and RNAIII. These results indicated that S. aureus coexisted in raw milk and goat farm environments, and also suggested the potential of luteolin as a promising antibiofilm agent against MDR S. aureus.

Antimicrobial and antibiofilm activity of isoorientin against carbapenem non-sensitive Escherichia coli from raw milk of goats.

Carbapenemase-producing E. coli is a grave public health concern as the potential emergence of resistant strains and their transmission. Isoorientin belongs to a potential antimicrobial flavonoid compound existing in several plants, while the research on the antimicrobial activity of isoorientin is limited thus far. We evaluated the antimicrobial and antibiofilm effects of isoorientin against biofilm-forming carbapenem non-sensitive Escherichia coli (E. coli) from raw milk of goats, and explored its molecular mechanisms. Isoorientin showed obvious antimicrobial ability with the minimum inhibitory concentration (MIC), and it exhibited synergistic activity with traditional antimicrobials against the carbapenem non-sensitive E. coli. Isoorientin could also significantly inhibit the carbapenem non-sensitive E. coli biofilm formation and destroy the established biofilms, with the percentage of inhibition ranging from 27.8% to 75% at MIC, and the corresponding percentage of eradication ranging from 15.3% to 61.6%, respectively. Confocal laser scanning microscopy (CLSM) observation and scanning electron microscopy (SEM) images indicated that the E. coli biofilm reduced in thickness with increasing concentrations of isoorientin. Dose-dependent decrease in eDNA revealed that isoorientin interacted with the extracellular polymeric substances (EPS) of the biofilm. qRT-PCR assay for the biofilm-forming associated genes further confirmed the above results. Overall, these results concluded that the isoorientin has significant antimicrobial and antibiofilm activity against carbapenem non-sensitive E. coli, and has potential application in prevention of food contamination and spoilage.

Escherichia coli (E. coli) has been the major foodborne bacteria that can cause diarrhea, gastroenteritis, and some complications, and also used as fecal bacteria pollution indicator in food. Carbapenems are considered as the last resort to life-threatening E. coli infections. We evaluated the antimicrobial and antibiofilm effects of isoorientin against biofilm-forming carbapenem non-sensitive E. coli from raw milk of goats, and explored its molecular mechanisms. This study firstly demonstrated the potential antimicrobial and antibiofilm properties of isoorientin against the carbapenem non-sensitive E. coli for the first time, and it has the properties of inhibiting the biofilm formation and destroying the preformed biofilms. Therefore, isoorientin is a promising biofilm inhibitor for curtailing drug resistant foodborne pathogens, and this study could provide a scientific basis for its practical application of isoorientin.

N6-methyladenosine-modified circular RNA QSOX1 promotes colorectal cancer resistance to anti-CTLA-4 therapy through induction of intratumoral regulatory T cells.

BACKGROUND: Colorectal cancer (CRC) is the 3rd most common cancer worldwide. CircRNAs are promising novel biomarkers for CRC. T regulatory (Treg) cells express the immune checkpoint receptor of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and promote tumor immunological tolerance. We therefore investigate the biological functions and mechanisms of circQSOX1 in CRC tumorigenesis; involvement of circQSOX1 in promoting Treg cell-mediated CRC immune escape in anti-CTLA-4 therapy. METHODS: Bioinformatics analyses were performed for circQSOX1expressions, specific binding sites, and N6-methyladenosine (m6A) motifs of circQSOX1, thatwere further validated with a series of experiments. Functions of circQSOX1 in promoting CRC development, Treg cells-based immune escape, and anti-CTLA-4 therapy response were investigated both in vitro and in vivo. RESULTS: High circQSOX1 expression was associated with carcinogenesis and poor clinical outcome of CRC patients. METTL3-mediated RNA m6A modification on circQSOX1 could be read by IGF2BP2 in CRC cells. CircQSOX1 promoted CRC development by regulating miR-326/miR-330-5p/PGAM1 axis. CircQSOX1 regulated glycolysis and promoted immune escape of CRC cells, and inhibits anti-CTLA-4 therapy response in CRC patients. CONCLUSION: m6A-modified circQSOX1 facilitated CRC tumorigenesis by sponging miR-326 and miR-330-5p to promotes PGAM1 expression, which further promoted CRC immune escape by activating glycolysis and inactivating the anti-CTLA-4 therapy response of CRC. Combined treatment with sh-circQSOX1 and anti-CTLA-4 could be a strategy to overcome Treg cell-mediated CRC immune therapy resistance.

Measurement of distal intramural spread and the optimal distal resection by naked eyes after neoadjuvant radiation for rectal cancers.

BACKGROUND: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. METHODS: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor's visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o'clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. RESULTS: At the distal 5, 6, and 7 o'clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was - 0.3 (95%CI - 4.0 ~ 3.4) mm, - 0.9 (95%CI - 3.4 ~ 1.7) mm, and - 0.4 (95%CI - 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. CONCLUSIONS: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.

The Classification and Surgical Treatments in Adult Hirschsprung's Disease: A Retrospective Study.

Purpose: To explore the treatments and short-term effects of different types of adult Hirschsprung's disease. Methods: 89 patients treated in Shanghai Changhai Hospital were retrospectively analyzed. According to the patient's medical history, clinical manifestations, auxiliary examination and postoperative pathological results, the patients were divided into adult congenital megacolon, adult idiopathic megacolon, ganglion cell deficiency (types I and II), toxic megacolon and iatrogenic megacolon, The Treatment methods and short-term prognosis of patients in each group were summarized. Results: 41 cases of Hirschsprung's disease in adults and low anterior resection or pull-out low anterior resection was performed, and 35 patients with idiopathic Megacolon were treated with one-stage subtotal colon resection under the condition of adequate preoperative preparation. Some patients admitted for emergency intestinal obstruction received conservative treatment first or underwent elective surgery after colonoscopic decompression was improved; two patients with ganglion cell deficiency subtotal colectomy were performed to remove the dilated proximal bowel segment and the narrow distal bowel segment; three patients with toxic Hirschsprung's disease underwent colostomy in mild cases, while subtotal colorectal resection was required in severe cases; Iatrogenic megacolon was diagnosed in eight cases and the optimum operation should be selected according to the specific conditions of patients. Conclusion: Adult Hirschsprung's diseases were divided into adult congenital hirschsprung's disease, idiopathic Hirschsprung's disease, ganglion cell deficiency, toxic hirschsprung's disease, and iatrogenic Hirschsprung's disease. Different types of surgical treatments for Hirschsprung's disease in adults should be selected according to the specific diagnosis. All patients with adult Hirschsprung's diseases have good short-term outcomes after surgical treatment.

Antibacterial and antibiofilm activity of Lagotis brachystachya extract against extended-spectrum ß-lactamases-producing Escherichia coli from broiler chickens.

Lagotis brachystachya Maxim (L. brachystachya) is an herb widely used in traditional Tibetan medicine. In the present study, the antibacterial activity of L. brachystachya extract to extended-spectrum-lactamases (ESBLs)-producing E. coli was determined by Kirby-Bauer disc diffusion, minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) methods as well as time-kill curve assay. Meanwhile, the biofilm inhibition and eradication effects of L. brachystachya extract on the ESBLs-producing E. coli were evaluated by crystal violet staining, and further confirmed by confocal laser scanning microscope (CLSM) and scanning electron microscopy (SEM). The results indicated that L. brachystachya extract exhibited moderate antibacterial activity, with diameter of inhibition zones varying from 15.4 to 20.3 mm, and the MIC and MBC values were 6.25 to 25 mg/mL and 12.5 to 100 mg/mL, respectively. Time-kill curve showed that 4 × MIC level of L. brachystachya extract concentration of was able to kill 99.9% of ESBLs-producing E. coli after 16 h treatment. The biofilm inhibition rate and eradication rate for the ESBLs-producing E. coli were 35.66 to 79.91% and 22.18 to 56.21% at MIC level of extract concentration, respectively. CLSM images showed that the biofilm became thinner as the ESBLs-producing E. coli isolate exposed to L. brachystachya extract with a concentration-dependent manner from 1/4 × MIC to MIC compared with the control isolate. SEM images indicated that L. brachystachya extract at 1/2 × MIC and MIC levels could evidently inhibit the biofilm formation or eradicate the mature biofilms. The effect of L. brachystachya highlights its potential of antibacterial and antibiofilm activities against the ESBLs-producing E. coli.

Dielectric-barrier discharge (DBD) plasma treatment reduces IgG binding capacity of ß-lactoglobulin by inducing structural changes.

The present study investigated the effects of dielectric-barrier-discharge (DBD) plasma treatment (12 kHz, 40 kV) at 1, 2, 3, and 4 min on the reduction of the immunoglobulin G (IgG) binding capacity of ß-lactoglobulin (ß-LG). The IgG binding capacity of ß-LG was reduced by 58.21% following a plasma treatment time of 4 min, as confirmed by western-blot and ELISA analyses. The reduction in IgG binding capacity of ß-LG was directly related to a stepwise change in its structure. The initial drop in the IgG binding capacity of ß-LG was found to be caused by conformational alteration, free sulfhydryl exposure and cross-linkage of molecules induced by oxidation of NH-/NH2- functional groups of peptide bonds and of sensitive amino acid residues (Tyr, Trp) as confirmed by SDS-PAGE, surface hydrophobicity and multi-spectroscopic analyses. Plasma treatment of more than 3 min resulted in cleavage of disulfidebonds and fragmentation of ß-LG that was confirmed by LC-MS/MS analysis, which resulted a further decline in the IgG binding capacity of ß-LG. Plasma treatment therefore has great potential as a substitute treatment for enzymatic hydrolysis for the production of hypoallergenic milk protein-based products.

Discovery and validation of methylation signatures in blood-based circulating tumor cell-free DNA in early detection of colorectal carcinoma: a case-control study.

BACKGROUND: Early detection of colorectal carcinoma (CRC) would help to identify tumors when curative treatments are available and beneficial. However, current screening methods for CRC, e.g., colonoscopy, may affect patients' compliance due to the uncomfortable, invasive and time-consuming process. In recent decades, methylation profiles of blood-based circulating tumor DNA (ctDNA) have shown promising results in the early detection of multiple tumors. Here we conducted a study to investigate the performance of ctDNA methylation markers in early detection of CRC. RESULTS: In total, 742 participants were enrolled in the study including CRC (n = 332), healthy control (n = 333), benign colorectal disease (n = 65) and advanced adenoma (n = 12). After age-matched and randomization, 298 participants (149 cancer and 149 healthy control) were included in training set and 141 (67 cancer and 74 healthy control) were in test set. In the training set, the specificity was 89.3% (83.2-93.7%) and the sensitivity was 88.6% (82.4-93.2%). In terms of different stages, the sensitivities were 79.4% (62.1-91.2%) in patients with stage I, 88.9% (77.3-95.8%) in patients with stage II, 91.4% (76.9-98.2%) in patients with stage III and 96.2% (80.3-99.9%) in patients with stage IV. Similar results were validated in the test set with the specificity of 91.9% (83.1-97.0%) and sensitivity of 83.6% (72.5-91.6%). Sensitivities for stage I-III were 87.0% (79.7-92.4%) in the training set and 82.5% (70.2-91.3%) in the test set, respectively. In the unmatched total population, the positive ratios were 7.8% (5.2-11.2%) in healthy control, 30.8% (19.9-43.5%) in benign colorectal disease and 58.3% (27.5-84.7%) in advanced adenoma, while the sensitivities of stage I-IV were similar with training and test sets. Compared with methylated SEPT9 model, the present model had higher sensitivity (87.0% [81.8-91.2%] versus 41.2% [34.6-48.1%], P < 0.001) under comparable specificity (90.1% [85.4-93.7%] versus 90.6% [86.0-94.1%]). CONCLUSIONS: Together our findings showed that ctDNA methylation markers were promising in the early detection of CRC. Further validation of this model is warranted in prospective studies.

Platelet indices in patients with acute appendicitis: a systematic review with meta-analysis.

Correlation between blood inflammatory parameters and acute appendicitis (AA) remains controversial. This meta-analysis aims to evaluate whether platelet (PLT) indices including mean platelet volume (MPV), PLT count, and platelet distribution width (PDW) are associated with AA. Pubmed, Embase, and Cochrane Library databases were searched for observational studies published from inception through April 2020 by two independent investigators. Studies reporting associations between platelet indices and AA were selected for inclusion. Standardized mean difference (SMD) and 95% confidence interval (CI) were estimated for continuous outcomes using a DerSimonian-Laird random-effects model. Of 842 records identified, 17 studies with a total of 6793 subjects met our inclusion criteria. Meta-analysis indicated that compared with those in healthy controls, significant decrease in MPV levels was observed in subjects with AA (SMD - 0.34; 95% CI - 0.56 to - 0.12; P = 0.003). Subgroup analyses represented a significant reduction of MPV levels in patients aged ≥ 30 years and non-complicated/non-perforated AA. Due to the small number of studies and patients included in each subgroup, these subgroup analyses need to be interpreted with caution. However, none of the levels of PLT (SMD - 0.13; 95% CI - 0.28-0.012; P = 0.071) or PDW (SMD 0.30; 95% CI - 0.22-0.83; P = 0.257) was seen decrease or increase in subjects with AA. This meta-analysis indicates a significant decrease in MPV levels in patients with AA, which makes MPV have the potential of serving as a biomarker for AA. The associations of other PLT indices with AA need to be further examined.

Rectal cancer patients with downstaging after neoadjuvant chemoradiotherapy and radical resection do not benefit from adjuvant chemotherapy.

BACKGROUND: Whether adjuvant chemotherapy is beneficial for rectal cancer patients who respond well to neoadjuvant chemoradiotherapy (NCRT) and undergo radical resection is controversial. This study aimed to assess the effect of adjuvant chemotherapy on the oncological outcomes of ypT0-2N0 rectal cancer patients after NCRT and radical resection, and identify the prognostic factors. METHODS: The clinical and pathological data of rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection between January, 2010 and June, 2018 were collected and retrospectively analyzed. The oncological outcomes of the chemotherapy (chemo) group and the non-chemotherapy (non-chemo) group were compared. Multivariate analysis, using a Cox proportional hazard model, was performed to identify independent predictors of oncological outcome. RESULTS: Of the 121 rectal cancer patients enrolled, 90 patients received postoperative adjuvant chemotherapy with no fewer than 3 cycles (the chemo group), and the other 31 patients with fewer than 3 cycles (the non-chemo group). There was no significant difference in the 5-year disease-free survival (DFS) or overall survival (OS) rates between the two groups (DFS: 79.1% vs. 82.9%, P=0.442; OS: 87.5% vs. 78.2%, P=0.667). cT4 is an independent risk factor for OS (HR =4.227, 95% CI: 1.128-15.838, P=0.02) and DFS (HR =4.878, 95% CI: 1.752-13.578). Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT significantly improved the DFS rate (HR =0.212, 95% CI: 0.058-0.776, P=0.019). CONCLUSIONS: Rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection did not benefit significantly from postoperative adjuvant chemotherapy. For these patients, cT4 was an independent risk factor for OS and DFS. Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT can significantly improve DFS.

Is the platelet to lymphocyte ratio a promising biomarker to distinguish acute appendicitis? Evidence from a systematic review with meta-analysis.

BACKGROUND: Although several previous studies have examined the association between the platelet to lymphocyte ratio (PLR) and acute appendicitis (AA), findings have been controversial. We aimed to systematically assess the available evidence to elucidate the overall relationship between the PLR and AA. METHODS: Pubmed and Embase databases were searched for all available published literature before August, 2019 by two independent investigators for observational studies reporting the association between the PLR and AA. Random effects models were applied for all meta-analyses. Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were calculated as effect estimates. RESULTS: Eleven articles met the inclusion criteria and included in this study. Meta-analysis showed that the level of PLR in the AA group was significantly higher than that in the control group (SMD: 1.19, 95% CI: 0.75 to 1.62, P<0.001). A series of subgroup analyses were conducted to investigate the heterogeneity, showing a significant increase in PLV levels in adults with age ≥30 years (SMD: 1.46, 95% CI: 0.89 to 2.02),compared to those in adult <30 years(SMD: 0.58, 95% CI: 0.12 to 1.04) or in children (SMD: 1.03, 95% CI: 0.51 to 1.56). Compared to non-AA controls, a significant increased PLR level was also observed in non-perforated AA (SMD: 1.23, 95% CI: 0.88 to 1.59) and in AA patients during pregnancy (SMD: 0.70, 95% CI: 0.36 to 1.04), while not in perforated AA (SMD: 2.28, 95% CI: -1.72 to 6.28). CONCLUSIONS: A significant increase in PLR level is found in patients with AA, indicating that PLR is a promising biomarker for AA. PLR provides a convenient option for emergency department to quickly screen for clinically or radiologically confirmed AA awaiting appendectomy, especially for pregnant women suspected of having AA. More high-quality evidence is needed to further confirm the diagnostic accuracy of PLR for AA.

[A single center retrospective study on surgical efficacy of T3NxM0 middle-low rectal cancer without neoadjuvant therapy].

OBJECTIVE: To investigate the surgical efficacy and prognostic factors of T3NxM0 middle-low rectal cancer without neoadjuvant therapy. METHODS: Clinical data of patients with middle-low rectal cancer undergoing TME surgery with T3NxM0 confirmed by postoperative pathology at Colorectal Surgery Department of Changhai Hospital from January 2008 to December 2010 were analyzed retrospectively. INCLUSION CRITERIA: (1)no preoperative neoadjuvant chemoradiotherapy (nCRT); (2) complete preoperative evaluation, including medical history, preoperative colonoscopy or digital examination, blood tumor marker examination, and imaging examination; (3) distance between tumor lower margin and anal verge was ≤ 10 cm; (4) negative circumferential resection margin (CRM-). Finally, a total of 331 patients were included in this study. According to the number of metastatic lymph node confirmed by postoperative pathology, the patients were divided into N0 group without regional lymph node metastasis (190 cases) and N+ group with regional lymph node metastasis (141 cases). The perioperative conditions, local recurrence, distant metastasis and prognostic factors were analyzed. RESULTS: Compared to N0 group in the perioperative data, N+ group had higher ratio of tumor deposit [29.8%(42/141) vs. 0, χ²=64.821, P<0.001] and vascular invasion [7.1%(10/141) vs. 0.5%(1/190),χ²=10.860, P<0.001]. There were no significant differences in tumor diameter, number of lymph nodes detected, positive nerve invasion, degree of tumor differentiation, morbidity of postoperative complication and postoperative adjuvant chemotherapy rate between the two groups (all P>0.05). The median follow-up period was 73.4 months. The merged 5-year local recurrence rate was 2.7%(9/331), 5-year distant metastasis rate was 23.3% (77/331), 5-year disease-free survival (DFS) rate was 73.4%, and 5-year overall survival (OS) rate was 77.2%. Multivariate analysis showed that lymph node metastasis (HR=3.120, 95%CI: 1.918 to 5.075, P<0.001), nerve invasion (HR=0.345, 95%CI: 0.156 to 0.760, P=0.008) and vascular invasion (HR=0.428, 95%CI: 0.189 to 0.972, P=0.043) were independent risk factors for DFS in patients with T3NxM0 rectal cancer after operation. Preoperative carcinoembryonic antigen level (HR=1.858, 95%CI:1.121 to 3.079, P=0.016), lymph node metastasis (HR=3.320, 95%CI: 1.985 to 5.553, P<0.001) and nerve invasion (HR=0.339, 95%CI: 0.156 to 0.738, P=0.006) were independent risk factors for OS in patients with T3NxM0 rectal cancer after operation. CONCLUSIONS: Optimal local control rate of middle-low rectal cancer patients with T3NxM0 and CRM- can be achieved by standard TME surgery alone. For patients with preoperative elevated blood carcinoembryonic antigen level, regional lymph node metastasis, or neurovascular invasion confirmed by pathology after surgery, adjuvant chemoradiotherapy should be actively applied after surgery to improve prognosis.

[Comparison of clinicopathological features and prognosis between left-sided colon cancer and right-sided colon cancer].

OBJECTIVE: To compare the clinicopathological features and prognosis between left-sided colon cancer (LC) and right-sided colon cancer (RC). METHODS: Clinicopathological and follow-up data of 2 174 colon carcinoma cases undergoing resection at Shanghai Changhai Hospital of The Second Military Medical University from January 2000 to December 2010 were retrospectively analyzed. Patients with transverse colon cancer, overlapping position, unknown location, recurrent cancer, multiple primary cancer, concomitant malignant tumors, preoperative chemotherapy, local resection, incomplete clinical data and missed follow up were excluded. Finally, a total of 1 036 patients, whose primary tumors were radically removed, were enrolled, with 563 patients in LC group (including carcinoma in cecum, ascending colon and hepatic flexure) and 473 in RC group (including carcinoma in splenic flexure, descending colon and sigmoid colon). The clinicopathological features and survival, including median overall survival, 5-year overall survival rate, tumor specific median overall survival, cancer specific 5-year overall survival rate, were compared between LC and RC groups. Tumor specific overall survival was defined as the period between operation date to the date of death caused by cancer progression. Multivariate Cox regression analysis was used to analyze the influencing factors of survival. Propensity score matching was carried out to balance the clinicopathological factors between the two groups with the SAS 9.3, taking the following parameters into consideration (age, gender, gross appearance, tumor diameter, invasion depth, lymph node metastasis, distant metastasis, TNM stages, differentiation, CEA and CA199-9). Patients in RC group and LC group were matched according to the propensity scores and the clinicopathological characteristics and prognosis of two groups were compared again. RESULTS: No significant differences were identified between the two groups in age, distant metastasis and serum CEA level. Compared with RC group, LC group had more male patients [60.9%(343/563) vs. 51.0%(241/473), P=0.001], more ulcerative tumors [71.9% (405/563) vs. 65.3%(309/473), P=0.006], better differentiation [well/moderately differentiated: 87.5%(493/563) vs. 73.8%(349/473), P=0.000], lower infiltration depth [T1-2: 17.1%(96/563) vs. 10.1%(48/473), P=0.001], higher lymph node metastasis rate [N0: 53.3%(300/563) vs. 62.4%(295/473), P=0.013], lower TNM stage [stage I(: 13.3%(75/563) vs. 7.8%(37/473), P=0.000], lower serum CA199 level [<37 kU/L: 68.4% (385/563) vs. 62.6% (296/473), P=0.022] and smaller tumor diameter [<5.0 cm: 55.1%(310/563) vs. 38.3%(181/473), P=0.000]. The median overall survival was 82 months and 76 months in LC and RC groups, respectively, and the 5-year overall survival rate was 58.3% and 50.9%(P=0.038). The median tumor specific survival was 84 months and 78 months in LC and RC groups, respectively, and the 5-year tumor specific overall survival rate was 60.6% and 52.9% (P=0.031). Multivariate Cox regression analysis showed that tumor location (LC vs. RC) was not associated with overall survival (P=0.106) and tumor specific survival (P=0.091). After propensity score matching, no significant difference was found in clinicopathological factors and propensity score (0.458±0.129 vs. 0.459±0.129, P=0.622) between LC and RC group. After matching, there was no significant difference in overall survival rate (54.0% vs. 51.7%, P=0.982) and tumor specific overall survival rate(56.4% vs. 53.1%, P=0.819) between two groups. CONCLUSION: Significant difference exists between RC and LC in clinicopathological factors, but not in survival.

Construction of cellulose based ZnO nanocomposite films with antibacterial properties through one-step coagulation.

Cellulose based ZnO nanocomposite (RCZ) films were prepared from cellulose carbamate-NaOH/ZnO solutions through one-step coagulation in Na2SO4 aqueous solutions. The structure and properties of RCZ films were characterized using XRD, FTIR, XPS, SEM, TEM, TG, tensile testing, and antibacterial activity tests. The content of ZnO in RCZ films was obtained in the range of 2.7-15.1 wt %. ZnO nanoparticles with a hexagonal wurtzite structure agglomerated into large particles, which firmly embedded in the cellulose matrix. RCZ films displayed good mechanical properties and high thermal stability. Moreover, the films exhibited excellent UV-blocking properties and antibacterial activities against Staphylococcus aureus and Escherichia coli. A dramatic reduction in viable bacteria was observed within 3 h of exposure, while all of the bacteria were killed within 6 h. This work provided a novel and simple pathway for the preparation of regenerated cellulose films with ZnO nanoparticles for application as functional biomaterials.

Lower rate of colonoscopic perforation: 110,785 patients of colonoscopy performed by colorectal surgeons in a large teaching hospital in China.

BACKGROUND: Colonoscopic perforation (CP) has a low incidence rate. However, with the extensive use of colonoscopy, even low incidence rates should be evaluated to identify and address risks. Information on CP is quite limited in China. OBJECTIVE: Our study aimed to determine the frequency of CP in colonoscopies performed by surgeons at a large teaching hospital in China over a 12-year period. METHODS: A retrospective review of medical records was performed for all patients who had CPs from 1 January 2000 to 31 December 2012. Iatrogenic perforations were identified mainly by abdominal X-ray or computed tomography scan. Follow-up information of adverse events post-colonoscopy was identified from the colorectal surgery database of our hospital. Patients' demographic data, colonoscopy procedure information, location of perforation, treatment, and outcome were recorded. RESULTS: A total of 110,785 diagnostic and therapeutic colonoscopy procedures were performed (86,800 diagnostic cases and 23,985 therapeutic cases) within the 12-year study period. A total of 14 incidents (0.012%) of CP were reported (seven males and seven females), of which nine cases occurred during diagnostic colonoscopy (0.01%) and five after therapeutic colonoscopy (three polypectomy cases, one endoscopic mucosal resection, and one endoscopic mucosal dissection). Mean patient age was 67.14 years. One case of CP (7.14%) after colonoscopy polypectomy was treated using curative colonoscopy endoclips. Other patients underwent operations: six cases (46.15%) of primary repair, four cases (28.57%) of resection with anastomosis, and two cases (15.38%) of resection without anastomosis. No obvious perforation was found in one patient (7.69%). Surgeons attempted to treat one case laparoscopically but eventually resorted to open surgery. The postoperative course was uncomplicated in eight cases (57.14%) and complicated in six cases (42.86%) but without mortality. CONCLUSION: CP is a serious but rare complication of colonoscopy. A perforation risk of 0.012% was found in our study. The optimal management of CP remains controversial. Treatment for CP should be individualized according to the patient's condition, related devices, and surgical skills of endoscopists or surgeons. Selective measures such as colonoscopy without intravenous sedation and decrease of loop formation can effectively reduce rates of perforation.

Decreased TIP30 expression predicts poor prognosis in pancreatic cancer patients.

Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive growth, and is characterized by early tissue invasion and metastasis with poor prognosis. Identifying prognostic markers and delineating the underlying mechanisms that promote progression of PDAC are important for the treatment of pancreatic cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple processes during tumor development and metastasis. Here, we investigated the expression of TIP30 in PDAC and its prognostic value in PDAC patients. We examined the expression of TIP30 by immunohistochemistry in tissue microarrays containing 106 surgically resected PDAC. Kaplan-Meier analysis and Cox proportional hazards regression modeling analysis showed that TIP30 expression independently predicted better survival in pancreatectomy patients (p < 0.01). Moreover, decreased TIP30 expression was associated with lymph node metastasis (p < 0.05) and loss of E-cadherin expression (r = 0.329, p < 0.01). Suppression of TIP30 resulted in upregulation of Snail and subsequent downregulation of E-cadherin in SW1990 cells containing high-level of endogenous TIP30. However, in the PANC-1 cells containing low level of endogenous TIP30, suppressing TIP30 caused upregulation of Slug instead of Snail, followed by upregulation of MMP9 rather than E-cadherin. Taken together, our work reveals that decreased TIP30 expression is able to enhance invasion and metastasis of pancreatic cancer cells through upregulation of the Snail family members and may serve as an independent predictor for poor outcomes in PDAC patients.

Dietary intake of vitamins A, C, and E and the risk of colorectal adenoma: a meta-analysis of observational studies.

To comprehensively summarize the association between dietary intake of vitamins A, C, and E and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer, relevant studies were identified in MEDLINE and EMBASE up to 31 October 2012. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I statistics. A total of 13 studies with 3832 CRA cases were included in this meta-analysis. On the basis of the highest versus lowest analysis, dietary intake of vitamin C reduced the risk of CRA by 22% (SRRs 0.78, 95% CIs: 0.62-0.98). Subgroup analyses showed that this relation was not modified by BMI, smoking status, and dietary energy intake. Further, dietary intake of ß-carotene was also inversely associated with the risk of CRA. However, dietary intake of vitamins A and E was not associated with the risk of CRA in overall and subgroup analyses (vitamin A: SRRs 0.87, 95% CIs: 0.67-1.14; vitamin E: SRRs 0.87, 95% CIs: 0.69-1.10). Our results indicate that dietary intake of vitamin C and ß-carotene, but not vitamins A and E, could reduce the risk of CRA. However, these associations seem to be limited. Further investigation using large samples and a rigorous methodology is warranted.