Effective glioblastoma immune sonodynamic treatment mediated by macrophage cell membrane cloaked biomimetic nanomedicines.

Glioblastoma (GBM) as one of the most lethal brain tumours, remains poor therapeutic index due to its typical characters including heterogeneous, severe immune suppression as well as the existence of blood brain barrier (BBB). Immune sonodynamic (ISD) therapy combines noninvasive sonodynamic therapy with immunotherapy, which has great prospects for the combinational treatment of GBM. Herein, we develop macrophage cell membrane cloaked reactive oxygen species (ROS) responsive biomimetic nanoparticles, co-delivering of sonosensitizer Ce6 and JQ1 (a bromo-domain protein 4 (BRD4) inhibitor which can down-regulate PD-L1) and realizing potent GBM ISD therapy. The ApoE peptide decorated macrophage membrane coating endows these biomimetic nanoparticles with low immunogenicity, efficient BBB permeability, prolonged blood circulation half-live and good biocompatibility. The ROS responsive polymeric inner core could be readily degraded as triggered by excessive ROS under the ultrasound once they accumulated in tumour cells, fast release encapsulated drugs. The generation of ROS not only killed tumour cells via sonodynamic therapy, but also induced immunogenic cell death (ICD) and further activated the anti-tumour immune response. The released JQ1 inhibited tumour cell proliferation and augmented the immune activities by inhibiting the PD-L1 expression on the surface of tumour cells. The cascade sonodynamic and immune therapy resulted in significantly improved median survival time in both orthotopic GL261 and PTEN deficient immunosuppressive CT2A GBM mice models. Therefore, our developed biomimetic nanoparticle platform provides a promising combinational therapy strategy to treat immune suppressive GBM.

A pan-cancer analysis for the oncogenic role of cyclin-dependent kinase inhibitor 1B in human cancers.

BACKGROUND: Human health and life are threatened by cancer with high morbidity and mortality worldwide. In many experiments, CDKN1B level is associated with cancer risk, Nevertheless, no pan-cancer analysis has been conducted on CDKN1B in human cancers. METHODS: With the help of bioinformatics, a pan-cancer analysis was conducted on the expression levels of CDKN1B in cancer tissues and adjacent tissues from the TCGA, CPTAC and GEO databases. The CDKN1B expression levels in tumor patients was further validated using immunohistochemistry (IHC) and quantitative real-time PCR. RESULTS: In the study, we first investigated the cancer-related roles of CDKN1B's in 40 tumors with malignancy. The CDKN1B gene encodes the p27Kip1 protein, which can block the production cyclin-dependent kinase (CDK), which is obviously related to the function and survival of cancer cells and alters the prognosis of cancer patients. Furthermore, CDKN1B function requires both protein processing and RNA metabolism. Additionally, the elevated expression of the CDKN1B gene and protein was validated in several cancer tissues from the patients. CONCLUSIONS: These results showed that the levels of CDKN1B were considerably different in a number of cancer tissues, offering a potential future target for cancer therapy.

Photophysical Exploration of Zn(II) Polypyridine Photosensitizers in Two-Photon Photodynamic Therapy: Insights from Theory.

The high incidence and difficulties of treatment of cancer have always been a challenge for mankind. Two-photon photodynamic therapy (TP-PDT) as a less invasive technique provides a new perspective for tumor treatment due to its low-energy near-infrared excitation, high targeting, and minor damage. At present, the emerging metal complexes used as the photosensitizers (PSs) in TP-PDT have aroused great interest. However, most metal complexes as PSs in TP-PDT still face some problems, such as slow clearance, unsatisfactory two-photon absorption (TPA) characteristics, high price, low reactivity, and poor solubility. In this work, density functional theory and time-dependent density functional theory were used to characterize the one/two-photon response, solvation free energy, and lipophilicity of a series of novel PSs applied in TP-PDT. The results suggest that based on complex 1, replacing Ru(II) center with Zn(II) (complex 2) can effectively prolong the triplet excited state lifetime while reducing the cost and environmental pollution, and the azetidine heterospirocycles were introduced into the ligand scaffold (complex 3), which effectively reduced the vibration relaxation of the ligand group and improved the water solubility; further, the addition of acetylenyl groups subtly enhanced the light absorption and significantly improved the two-photon response (complex 4). In addition, all complexes met the requirement of a PS and could be used as potential candidates for TP-PDT. In particular, complex 4 has the advantages of high solvation free energy, a large TPA cross-section (1413 GM), a long triplet state lifetime (671 µs), good chemical reactivity, and low cost, and it is easy to be scavenged by organisms. Overall, this contribution may provide an important clue to formulate clear design principles for type I/II PSs and rational design of PSs with high intersystem crossing rates, a long lifetime, and therapeutic excitation wavelengths.

A Theoretical Investigation into the Homo- and Hetero-leptic Cu(I) Phosphorescent Complexes Bearing 2,9-dimethyl-1,10-phenanthroline and bis [2-(diphenylphosphino)phenyl]ether Ligand.

Cu(I) complexes have received widespread attention as a promising alternative to traditional noble-metal complexes. Herein, we systematically study the properties of Cu(I) complexes from homo- to hetero-ligands, and found the following: (1) hetero-ligands are beneficial to regulate phosphorescent efficiency; (2) when the hetero-ligands in a tetracoordinated Cu(I) complex are 1:1, the ligands coordinate along the dx2-y2 direction of Cu(I) ion, which can observably suppress structural deformation; (3) unlike the P^P ligand, the N^N ligand can enhance the participation of Cu(I) during the transition process; (4) the addition of an appropriate amount of P^P ligand can effectively raise the energy level of HOMO (highest occupied molecular orbital), enhance the proportion of LLCT (ligand-ligand charge transfer), and thereby increase the available singlet emission transition moments which can be borrowed, thus promoting the radiative decay process. As a result, this work provides a detailed understanding of the effects of different ligands in Cu(I) complexes, and provides a valuable reference and theoretical basis for regulating and designing the phosphorescent properties of Cu(I) complexes in the future.

Maternal Dietary Forsythia suspensa Extract Supplementation Induces Changes in Offspring Antioxidant Status, Inflammatory Responses, Intestinal Development, and Microbial Community of Sows.

This experiment aims to investigate the effect of maternal diet supplemented with Forsythia suspensa extract (FSE) on the performance, antioxidant status, inflammatory responses, intestinal development, and microbial community of sows. A total of 24 gestating sows (Landrace × Yorkshire) were assigned to 2 treatments with 12 sows per treatment. From d 107 of gestation to d 21 of lactation, sows were supplemented with a basal diet as control (CON) or an FSE diet (basal diet + 100 mg/kg FSE). Compared with CON, sows fed FSE showed lower (P < 0.05) wean-to-estrus interval, body weight loss, and higher (P < 0.05) average daily gain of suckling piglet. Sows fed FSE had reduced (P < 0.05) serum malondialdehyde (MDA) content and enhanced (P < 0.05) catalase and glutathione peroxidase (GSH-Px) contents at farrowing and weaning compared with CON. The suckling piglets of FSE-fed sows had increased (P < 0.05) mRNA expressions of nuclear factor erythroid-2 related factor 2, heme oxygenase-1 in the liver, and lower (P < 0.05) serum MDA content on d 0, 7, and 14 of lactation. Sows fed FSE had lower (P < 0.05) serum tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) contents at farrowing and reduced (P < 0.05) serum IL-6 and IL-8 contents at weaning compared with CON. Piglets from FSE-fed sows had enhanced (P ≤ 0.05) villus height and villus height to crypt depth ratio in the jejunum, and higher (P < 0.05) protein expression of Occludin in jejunal mucosa compared with CON. Sows fed FSE tended to have higher (P = 0.09) relative abundance of Lactobacillus at genus level in feces at weaning compared with CON. Our results showed maternal diet supplemented with FSE in lactating sows could effectively induce improvement of performance, antioxidant status, anti-inflammatory function, intestinal morphology, barrier function, and microbial community.

Charge-based drug delivery to cartilage: Hydrophobic and not electrostatic interactions are the dominant cause of competitive binding of cationic carriers in synovial fluid.

Charge-based drug delivery has proven to be effective for targeting negatively charged cartilage for the treatment of osteoarthritis. Cartilage is surrounded by synovial fluid (SF), which is comprised of negatively charged hyaluronic acid and hydrophobic proteins that can competitively bind cationic carriers and prevent their transport into cartilage. Here we investigate the relative contributions of charge and hydrophobic effects on the binding of cationic carriers within healthy and arthritic SF by comparing the transport of arginine-rich cartilage targeting cationic peptide carriers with hydrophilic (CPC +14N) or hydrophobic property (CPC +14A). CPC +14N had significantly greater intra-cartilage uptake in presence of SF compared to CPC +14A in-vitro and in vivo. In presence of individual anionic SF constituents, both CPCs maintained similar high intra-cartilage uptake while in presence of hydrophobic constituents, CPC +14N had greater uptake confirming that hydrophobic and not charge interactions are the dominant cause of competitive binding within SF. Results also demonstrate that short-range effects can synergistically stabilize intra-cartilage charge-based binding - a property that can be utilized for enhancing drug-carrier residence time in arthritic cartilage with diminished negative fixed charge density. The work provides a framework for the rational design of cationic carriers for developing targeted therapies for another complex negatively charged environments. STATEMENT OF SIGNIFICANCE: This work demonstrates that hydrophobic and not charge interactions are the dominant cause of the binding of cationic carriers in synovial fluid. Therefore, cationic carriers can be effectively used for cartilage targeting if they are made hydrophilic. This can facilitate clinical translation of various osteoarthritis drugs for cartilage repair that have failed due to a lack of effective cartilage targeting methods. It also demonstrates that short-range hydrogen bonds can synergistically stabilize electrostatic binding in cartilage offering a method for enhancing the targeting and residence time of cationic carriers within arthritic cartilage with reduced charge density. Finally, the cartilage-synovial fluid unit provides an excellent model of a complex negatively charged environment and allows us to generalize these findings and develop targeted therapies for other charged tissue-systems.

Cationic peptide carriers enable long-term delivery of insulin-like growth factor-1 to suppress osteoarthritis-induced matrix degradation.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) has the potential to be used for osteoarthritis (OA) treatment but has not been evaluated in clinics yet owing to toxicity concerns. It suffers from short intra-joint residence time and a lack of cartilage targeting following its intra-articular administration. Here, we synthesize an electrically charged cationic formulation of IGF-1 by using a short-length arginine-rich, hydrophilic cationic peptide carrier (CPC) with a net charge of +14, designed for rapid and high uptake and retention in both healthy and arthritic cartilage. METHODS: IGF-1 was conjugated to CPC by using a site-specific sulfhydryl reaction via a bifunctional linker. Intra-cartilage depth of penetration and retention of CPC-IGF-1 was compared with the unmodified IGF-1. The therapeutic effectiveness of a single dose of CPC-IGF-1 was compared with free IGF-1 in an IL-1α-challenged cartilage explant culture post-traumatic OA model. RESULTS: CPC-IGF-1 rapidly penetrated through the full thickness of cartilage creating a drug depot owing to electrostatic interactions with negatively charged aggrecan-glycosaminoglycans (GAGs). CPC-IGF-1 remained bound within the tissue while unmodified IGF-1 cleared out. Treatment with a single dose of CPC-IGF-1 effectively suppressed IL-1α-induced GAG loss and nitrite release and rescued cell metabolism and viability throughout the 16-day culture period, while free IGF at the equivalent dose was not effective. CONCLUSIONS: CPC-mediated depot delivery of IGF-1 protected cartilage by suppressing cytokine-induced catabolism with only a single dose. CPC is a versatile cationic motif that can be used for intra-cartilage delivery of other similar-sized drugs.

DDX10 promotes the proliferation and metastasis of colorectal cancer cells via splicing RPL35.

BACKGROUND: Colorectal cancer (CRC) has become the second deadliest cancer in the world and severely threatens human health. An increasing number of studies have focused on the role of the RNA helicase DEAD-box (DDX) family in CRC. However, the mechanism of DDX10 in CRC has not been elucidated. METHODS: In our study, we analysed the expression data of CRC samples from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Subsequently, we performed cytological experiments and animal experiments to explore the role of DDX10 in CRC cells. Furthermore, we performed Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analyses. Finally, we predicted the interacting protein of DDX10 by LC-MS/MS and verified it by coimmunoprecipitation (Co-IP) and qPCR. RESULTS: In the present study, we identified that DDX10 mRNA was extremely highly expressed in CRC tissues compared with normal colon tissues in the TCGA and GEO databases. The protein expression of DDX10 was measured by immunochemistry (IHC) in 17 CRC patients. The biological roles of DDX10 were explored via cell and molecular biology experiments in vitro and in vivo and cell cycle assays. We found that DDX10 knockdown markedly reduced CRC cell proliferation, migration and invasion. Then, we constructed a PPI network with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA) showed that DDX10 was closely related to RNA splicing and E2F targets. Using LC-MS/MS and Co-IP assays, we discovered that RPL35 is the interacting protein of DDX10. In addition, we hypothesize that RPL35 is related to the E2F pathway and the immune response in CRC. CONCLUSIONS: In conclusion, provides a better understanding of the molecular mechanisms of DDX10 in CRC and provides a potential biomarker for the diagnosis and treatment of CRC.

Dietary live yeast supplementation alleviates transport-stress-impaired meat quality of broilers through maintaining muscle energy metabolism and antioxidant status.

BACKGROUND: This experiment was to investigate the effect of dietary live yeast (LY, 1 × 1010 CFU g-1 ) supplementation on serum metabolic parameters, meat quality as well as antioxidant enzyme activity of transported broilers. A total of 192 one-day-old broilers were randomly assigned to four treatments with six replicates and eight chicks per replicate: a basal diet without transportation (CON), a basal diet containing 0 (T), 500 (T + LY500 ) and 1000 mg kg-1 (T + LY1000 ) LY with 3 h of transportation after feeding for 42 days, respectively. The serum and muscle samples of broilers were collected immediately after 3 h of transportation. RESULTS: A higher (P < 0.05) final body weight and average daily weight gain were observed in T + LY1000 group compared with CON and T groups. The T + LY1000 group reduced (P < 0.05) the serum lactate contents and improved (P < 0.05) the pH24h and decreased (P < 0.05) the drip loss in muscles of transported-broilers. Also, the T + LY1000 group enhanced (P < 0.05) the total-antioxidant capacity and reduced (P < 0.05) the malondialdehyde in serum and muscles. Besides, the messenger RNA (mRNA) expression of avian uncoupling protein (avUCP) in muscles was down-regulated (P < 0.05) of T + LY1000 group compared with T group. CONCLUSION: Dietary LY supplementation alleviates transport-stress-impaired meat quality of broilers through maintaining muscle energy metabolism and antioxidant status. Therefore, LY may serve as a potential protector for broilers under transport stress in the future. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The gut microbial diversity of colon cancer patients and the clinical significance.

The microbial diversity and communities in the excrement of healthy and patients suffered from cancer were identified by 16SrDNA sequencing performed on the Illumina Hi Seq sequencing platform. The microbial difference was also analyzed. The sequencing results showed high quality of the data, and the microbial communities were more various in the excrement of cancer patients. And the abundance of Firmicutes phylum was significantly reduced in cancer group. The phylum of Fermicutes, Bacteroidetes in cancer group are significantly down-regulated and up-regulated compared with normal group. The species of Faecalibacterium prausnitzii, Bateroides vulgatus and Fusicatenibacter saccharivorans are significantly lower in cancer group than that in normal group (P< 0.05). The species of Prevetella copri, M. uniformis, and Escherichia coli are significantly higher in the cancer group than that in normal group. The comparative results indicated that beneficial bacterium significantly decreased in colorectal cancer (CRC) group, and harmful bacterium significantly increased in the colon cancer group, meanwhile the acidity, sugar increased whereas the oxygen content decreased to facilitate the growth of harmful bacterium. The results would provide microbial approaches for the treatment of colon cancer by the intake of beneficial microbial communities.

Discrimination of False Negative Results in RT-PCR Detection of SARS-CoV-2 RNAs in Clinical Specimens by Using an Internal Reference.

Reverse transcription-polymerase chain reaction (RT-PCR) is an essential method for specific diagnosis of SARS-CoV-2 infection. Unfortunately, false negative test results are often reported. In this study, we attempted to determine the principal causes leading to false negative results of RT-PCR detection of SARS-CoV-2 RNAs in respiratory tract specimens. Multiple sputum and throat swab specimens from 161 confirmed COVID-19 patients were tested with a commercial fluorescent RT-PCR kit targeting the ORF1ab and N regions of SARS-CoV-2 genome. The RNA level of a cellular housekeeping gene ribonuclease P/MRP subunit p30 (RPP30) in these specimens was also assessed by RT-PCR. Data for a total of 1052 samples were retrospectively re-analyzed and a strong association between positive results in SARS-CoV-2 RNA tests and high level of RPP30 RNA in respiratory tract specimens was revealed. By using the ROC-AUC analysis, we identified Ct cutoff values for RPP30 RT-PCR which predicted false negative results for SARS-CoV-2 RT-PCR with high sensitivity (95.03%-95.26%) and specificity (83.72%-98.55%) for respective combination of specimen type and amplification reaction. Using these Ct cutoff values, false negative results could be reliably identified. Therefore, the presence of cellular materials, likely infected host cells, are essential for correct SARS-CoV-2 RNA detection by RT-PCR in patient specimens. RPP30 could serve as an indicator for cellular content, or a surrogate indicator for specimen quality. In addition, our results demonstrated that false negativity accounted for a vast majority of contradicting results in SARS-CoV-2 RNA test by RT-PCR.

Effects of dietary fiber sources during late gestation and lactation on sow performance, milk quality, and intestinal health in piglets1.

This study was conducted to investigate the effects of dietary supplementation with 2 sources of fiber, sugar beet pulp (SBP), and wheat bran (WB), on sow performance, milk quality, and intestinal health in piglets. Forty-five multiparous sows at day 85 of gestation were allocated to the following 3 treatments: 1) a corn-soybean meal basal diet (CON); 2) the CON diet supplemented with 20% SBP in gestation and 10% SBP in lactation (SBP); and 3) the CON diet supplemented with 30% WB in gestation and 15% WB in lactation (WB). The SBP diets increased (P < 0.05) sow ADFI during lactation, litter and piglet weaning weight, piglet ADG, immunoglobulin A (IgA), and interleukin-10 (IL-10) levels in the colostrum and IgA levels in the milk, while the WB diets only increased (P < 0.05) IL-10 levels in the milk when compared with the CON diets. Piglets from SBP-fed sows had greater (P < 0.05) serum growth hormone and insulin-like growth factor-1 levels than those from WB-fed or CON-fed sows, whereas piglets from WB-fed sows had greater (P < 0.05) serum GH levels than those from CON-fed sows. Serum diamine oxidase activity, endotoxin, IL-6, and tumor necrosis factor-α (TNF-α) levels were reduced (P < 0.05) in piglets from SBP-fed or WB-fed sows. Piglets from SBP-fed sows also had greater (P < 0.05) serum IL-10 levels than those from CON-fed sows. The ileal mRNA expression of TNF-α was reduced (P < 0.05) in piglets from SBP-fed or WB-fed sows. Piglets from SBP-fed sows had lower (P < 0.05) IL-6 expression, and greater (P < 0.05) IL-10 expression and secretory immunoglobulin A (SIgA) levels in the ileum than those from WB- or CON-fed sows. Piglets from WB-fed sows had greater (P < 0.05) IL-10 expression and SIgA levels compared with those from CON-fed sows. The ileal mRNA expression of occludin in the ileum was greater (P < 0.05) in piglets from SBP-fed sows than those from CON-fed sows. The ileal mRNA expression of ZO-1 was greater (P < 0.05) in piglets from WB-fed sows than those from CON-fed sows, but lower (P < 0.05) than those from SBP-fed sows. Piglets from SBP-fed sows had greater (P < 0.05) abundance of Christensenellaceae and butyrate levels in the colon, while piglets from WB-fed sows had greater (P < 0.05) abundance of Lactobacillaceae. Collectively, maternal SBP supplementation was more effective than WB in improving milk quality, enhancing growth performance and intestinal barrier function, and ameliorating intestinal inflammation in piglets.

Cartilage penetrating cationic peptide carriers for applications in drug delivery to avascular negatively charged tissues.

Drug delivery to avascular, negatively charged tissues like cartilage remains a challenge. The constant turnover of synovial fluid results in short residence time of administered drugs in the joint space and the dense negatively charged matrix of cartilage hinders their diffusive transport. Drugs are, therefore, unable to reach their cell and matrix targets in sufficient doses, and fail to elicit relevant biological response, which has led to unsuccessful clinical trials. The high negative fixed charge density (FCD) of cartilage, however, can be used to convert cartilage from a barrier to drug entry into a depot by making drugs positively charged. Here we design cartilage penetrating and binding cationic peptide carriers (CPCs) with varying net charge, spatial distribution and hydrophobicity to deliver large-sized therapeutics and investigate their electro-diffusive transport in healthy and arthritic cartilage. We showed that CPC uptake increased with increasing net charge up to +14 but dropped as charge increased further due to stronger binding interactions that hindered CPC penetrability and uptake showing that weak-reversible binding is key to enable their penetration through full tissue thickness. Even after 90% GAG depletion, while CPC +14 uptake reduced by over 50% but still had a significantly high value of 148× showing that intra-tissue long-range charge-based binding is further stabilized by short-range H-bond and hydrophobic interactions. The work presents an approach for rational design of cationic carriers based on tissue FCD and properties of macromolecules to be delivered. These design rules can be extended to drug delivery for other avascular, negatively charged tissues. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) remains an untreatable disease partly due to short joint residence time of drugs and a lack of delivery methods that can effectively target the dense, avascular, highly negatively charged cartilage tissue. In this study, we designed cartilage penetrating and binding cationic peptide carriers (CPCs) that, due to their optimal charge provide adequate electrical driving force to rapidly transport OA drugs into cartilage and reach their cell and matrix targets in therapeutic doses before drugs exit the joint space. This way cartilage is converted from being a barrier to drug entry into a drug depot that can provide sustained drug release for several weeks. This study also investigates synergistic effects of short-range H-bond and hydrophobic interactions in combination with long-range electrostatic interactions on intra-cartilage solute transport. The work provides rules for rational design of cartilage penetrating charge-based carriers depending on the net charge of tissue (normal versus arthritic), macromolecule to be delivered and whether the application is in drug delivery or tissue imaging.

Anti-metastatic activity of fangchinoline in human gastric cancer AGS cells.

Fangchinoline (FCL) is an active component isolated from the traditional medicinal plant Stephania tetrandra S. Moore, and has been reported to possess anti-cancer functions in several types of cancers; however, the effect of FCL on gastric cancer metastasis and its underlying molecular mechanisms remain unknown. The current study aimed to investigate the effect of FCL on the cell migration and invasion of human metastatic gastric cancer AGS cells and its mechanisms. Our study demonstrates that FCL dosage dependently suppressed the adhesion, migration and invasion capacities of human gastric cancer AGS cells without obvious cytotoxic effects. Reverse transcription-polymerase chain reaction and western blot assays demonstrated that FCL greatly inhibited the expression of matrix metalloproteinase (MMP)-2 and MMP-9 at both the mRNA and protein levels, while it significantly increased the expression of tissue inhibitor of metalloproteinase (TIMP) 1 and TIMP2 messenger RNAs. Our results also indicated that FCL repressed the phosphorylation of AKT in gastric cancer AGS cells. In summary, FCL may exert its anti-metastatic property in human gastric cancer cells in vitro by suppression of MMP-2 and MMP-9, increase of TIMP1 and TIMP2 genes, and inhibition of AKT phosphorylation. FCL may be a drug candidate for the treatment of gastric cancer metastasis.

A comparative study of small intestinal perforation secondary to foreign body and other non-traumatic causes.

BACKGROUND: Little was known about gastrointestinal perforation secondary to foreign body in adults, which was only documented by several case series reports. The aim of this study was to characterize it with comparative methods. METHODS: A retrospective study was conducted on twenty patients with the diagnosis of gastrointestinal perforation secondary to foreign body between January 2003 and October 2013. The perforations were all located in the small intestine and compared to eighty-seven patients with non-traumatic small intestinal perforation. RESULTS: 35% of the patients in the foreign body group were over 65 years of age, which is much higher than the local elderly population ratio (p=0.002). In the foreign body group, more patients presented without diffuse abdominal physical signs (p=0.008) and preoperational CT scans had higher accuracy (p=0.027). Perforation repair was performed more often (p=0.024). Mean MPI was 19.9 and the morbidity rate was 35%, significantly lower than in the cases of other causes (p=0.001, 0.041). Mean duration of hospitalization was 11.5 days and was shorter compared to other causes (p=0.038). CONCLUSION: Clinical performance of small intestinal perforation secondary to foreign body is atypical, and preoperative diagnosis relies on CT scans. Primary perforation closure is safe and effective, and relatively better outcomes can be achieved.

Proximal gastrectomy versus total gastrectomy for proximal gastric carcinoma. A meta-analysis on postoperative complications, 5-year survival, and recurrence rate.

OBJECTIVE: To compare proximal gastrectomy (PG) with total gastrectomy (TG) for proximal gastric carcinoma, through the 5-year survival rate, recurrence rate, postoperative complications, and long-term life quality. METHODS: The meta-analysis was carried out in the General Surgery Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. We searched Medline, EMBASE, and the Cochrane Library from June to November 2012. The literature searches were carried out using medical subject headings and free-text word: `proximal gastrectomy` `total gastrectomy` `partial gastrectomy` `stomach neoplasms` and `gastric cancer`. Two different reviewers carried out the search and evaluated studies independently. RESULTS: Two randomized controlled trials and 9 retrospective studies were included. A total of 1364 patients were included in our study. Our analysis showed that there is no statistically significant difference in 5-year survival rate between PG and TG (60.9% versus 64.4%). But, the recurrence is higher in the PG group than the TG (38.7% versus 24.4%). The anastomotic stenosis rate is also higher in the PG than the TG (27.4% versus 7.4%). CONCLUSION: Proximal gastrectomy is an option for upper third gastric cancer in terms of safety. However, it is associated with high risk of reflux symptoms and anastomotic stenosis. Therefore, TG should be the first choice for proximal gastric cancer to prevent reflux symptoms.

[Correlation of single nucleotide polymorphisms of X-ray repair cross complementing group 1 gene to hereditary susceptibility of colorectal cancer].

OBJECTIVE: To investigate the correlation of single nucleotide polymorphisms (SNP) of XRCC1 gene to hereditary susceptibility of colorectal cancer. METHODS: XRCC1 genotypes in 124 colorectal cancer patients and 214 matched healthy people as control were analyzed by SnaP Shot SNP-typing technique. Five different inheritance models including codominant, dominant, recessive, overdominant and log-additive were analyzed using logistic regression model. The haplotype distribution was estimated with phase and its correlation with the risk of colorectal cancer was evaluated. RESULTS: The frequencies of mutant 25487G-A, 25489C-T and 1799782C-T alleles were 0.20, 0.11, 0.32 respectively in the patients, and 0.23, 0.13, 0.34 in the controls. There was no significant correlation of polymophisms of XRCC1 gene to the risk of colorectal cancer in 5 different inheritance models (P>0.05). GCT, GCC, ACC and GTC were the most common haplotypes and the odds ratios were 1, 1.35, 0.90 and 0.84 respectively. There was no significant difference of distribution between 2 groups in haplotypes. CONCLUSION: Polymorphisms of XRCC1 gene, including rs25487, rs25489, rs1799782, are not associated with to the risk of colorectal cancer.