[Clinical and radiologic comparison between oblique lateral interbody fusion and minimally invasive transforaminal lumbar interbody fusion for degenerative lumbar spondylolisthesis].

OBJECTIVE: To compare the short-term clinical efficacy and radiologic differences between oblique lateral interbody fusion(OLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for degenerative lumbar spondylolisthesis. METHODS: A retrospective analysis was performed on 58 patients with lumbar spondylolisthesis treated with OLIF or MIS-TLIF from April 2019 to October 2020. Among them, 28 patients were treated with OLIF (OLIF group), including 15 males and 13 females aged 47 to 84 years old with an average age of (63.00±9.38) years. The other 30 patients were treated with MIS-TLIF(MIS-TLIF group), including 17 males and 13 females aged 43 to 78 years old with an average age of (61.13±11.10) years. General conditions, including operation time, intraoperative blood loss, postoperative drainage, complications, lying in bed, and hospitalization time were recorded in both groups. Radiological characteristics, including intervertebral disc height (DH), intervertebral foramen height (FH), and lumbar lordosis angle (LLA), were compared between two groups. The visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate the clinical effect. RESULTS: The operation time, intraoperative blood loss, postoperative drainage, lying in bed, and hospitalization time in OLIF group were significantly less than those in the MIS-TLIF group (P<0.05). The intervertebral disc height and intervertebral foramen height were significantly improved in both groups after the operation (P<0.05). The lumbar lordosis angle in OLIF group was significantly improved compared to before the operation(P<0.05), but there was no significant difference in the MIS-TLIF group before and after operation(P>0.05). Postoperative intervertebral disc height, intervertebral foramen height, and lumbar lordosis were better in the OLIF group than in the MIS-TLIF group (P<0.05). The VAS and ODI of the OLIF group were lower than those of the MIS-TLIF group within 1 week and 1 month after the operation (P<0.05), and there were no significant differences in VAS and ODI at 3 and 6 months after the operation between the two groups(P>0.05). In the OLIF group, 1 case had paresthesia of the left lower extremity with flexion-hip weakness and 1 case had a collapse of the endplate after the operation;in the MIS-TLIF group, 2 cases had radiation pain of lower extremities after decompression. CONCLUSION: Compared with MIS-TLIF, OLIF results in less operative trauma, faster recovery, and better imaging performance after lumbar spine surgery.

Synthesis and Antibacterial Activity Evaluation of Biphenyl and Dibenzofuran Derivatives as Potential Antimicrobial Agents against Antibiotic-Resistant Bacteria.

The escalating prevalence of antibiotic-resistant bacteria has led to a serious global public health problem; therefore, there is an urgent need for the development of structurally innovative antibacterial agents. In our study, a series of biphenyl and dibenzofuran derivatives were designed and synthesized by Suzuki-coupling and demethylation reactions in moderate to excellent yields (51-94% yield). Eleven compounds exhibited potent antibacterial activities against the prevalent antibiotic-resistant Gram-positive and Gram-negative pathogens, among which compounds 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (6i) and 5-(9H-carbazol-2-yl) benzene-1,2,3-triol (6m) showed the most potent inhibitory activities against methicillin-resistant Staphylococcus aureus and multidrug-resistant Enterococcus faecalis with MIC (minimum inhibitory concentration) values as low as 3.13 and 6.25 µg/mL, respectively. Compounds 3',5'-dimethyl-[1,1'-biphenyl]-3,4,4',5-tetraol (6e), 4'-fluoro-[1,1'-biphenyl]-3,4,5-triol (6g), and 4'-(trifluoromethyl)-[1,1'-biphenyl]-3,4,5-triol (6i) showed comparable inhibitory activities with ciprofloxacin to Gram-negative bacterium carbapenems-resistant Acinetobacter baumannii. Study of the structure-activity relationship indicated that a strong electron-withdrawing group on the A ring and hydroxyl groups on the B ring of biphenyls were beneficial to their antibacterial activities, and for benzo-heterocycles, N-heterocycle exhibited optimal antibacterial activity. These results can provide novel structures of antibacterial drugs chemically different from currently known antibiotics and broaden prospects for the development of effective antibiotics against antibiotic-resistant bacteria.

Chemokines in colon cancer progression.

Colon cancer is a major human cancer accounting for about a tenth of all cancer cases thus making it among the top three cancers in terms of incidence as well as mortality. Metastasis to distant organs, particularly to liver, is the primary reason for associated mortality. Chemokines, the chemo-attractants for various immune cells, have increasingly been reported to be involved in cancer initiation and progression, including in colon cancer. Here we discuss the available knowledge on the role of several chemokines, such as, CCL2, CCL3, CCL5, CXCL1, CXCL2, CXCL8 in colon cancer progression. CCL20 is one chemokine with emerging evidence for its role in influencing colon cancer tumor microenvironment through the documents effects on fibroblasts, macrophages and immune cells. We focus on CCL20 and its receptor CCR6 as promising factors that affect multiple levels of colon cancer progression. They interact with several cytokines and TLR receptors leading to increased aggressiveness, as supported by multitude of evidence from in vitro, in vivo studies as well as human patient samples. CCL20-CCR6 bring about their biological effects through regulation of several signaling pathways, including, ERK and NF-κB pathways, in addition to the epithelial-mesenchymal transition. Signaling involving CCL20-CCR6 has profound effect on colon cancer hepatic metastasis. Combined with elevated CCL20 levels in colon tumors and metastatic patients, the above information points to a need for further evaluation of chemokines as diagnostic and/or prognostic biomarkers.

Exosomal miR-21 promotes proliferation, invasion and therapy resistance of colon adenocarcinoma cells through its target PDCD4.

Exosomes contain cell-specific collections of bioactive materials including proteins, lipids, and RNAs that are transported to recipient cells to exert their impacts. MicroRNAs (miRNAs) can function as tumor suppressor or oncogenic genes and miR-21 is one of the most frequently up-regulated miRNAs in solid tumors including colon cancer. The aim of this study was to investigate the role of miR-21, secreted from exosomes, in proliferation and invasion of colon cancer, along with the mechanistic details. We used a variety of biochemical techniques including ultracentrifugation-based exosome purification, electron transmission microscopy, western blot and RT-qPCR to detect the expression levels of miR-21 in exosomes purified from culture media of human colonic adenocarcinoma cell lines. We then performed functional and mechanistic studies using three colon cancer cell lines HT29, T84 and LS174 as well as the normal colon epithelial cells CRL1831. miR-21 target PDCD4 was investigated for its role in mediating miR-21 effects. Expression of miR-21 was significantly up-regulated in exosomes of colon cancer cells, compared to the normal human colon epithelial cells. Treatment of colon cancer cells with isolated exosomes or miR-21 led to an increased expression of genes involved in cell proliferation, invasion and extracellular matrix formation. miR-21 targets PDCD4, TPM1 and PTEN were down-regulated by exosomes and silencing of PDCD4 mimicked miR-21 functional effects, even the induced resistance against 5-FU. Our study suggests that targeted inhibition of exosomes, particularly those carrying miR-21, may represent a novel approach for treatment of colorectal cancer.

A review on the efficacy and safety of iodine-125 seed implantation in unresectable pancreatic cancers.

Background: Pancreatic cancers are the common digestive system tumors with poor prognosis and due to its late diagnosis, surgical resection does not remain a viable treatment option in about 80% of patients. Amongst different treatment options, radioactive 125I seed implantation therapy has also emerged as a good alternative in non-resectable pancreatic cancer patients.Purpose: The present review describes the efficacy and safety of iodine-125 seed implantation in unresectable pancreatic cancers in preclinical and clinical studies.Results: In this technique, small radioactive particles are implanted inside the tumor cells to produce the sustain effects. Due to the short radial distance of these radiations, there is a selective and efficient killing of cancer cells without any significant injury to the neighboring cells. Amongst the different methods for implanting 125I seeds in the pancreatic tissues, CT scan or ultrasound-guided percutaneous seed implantation is preferred as it offers shorter operative time, lesser bleeding, early recovery, lesser complications, and low medical costs. The clinical studies have shown that radioactive 125I seed implantation is a good option for the management of local tumor growth, pain palliation, and improvement in the life span of patients suffering from unresectable pancreatic cancer.Conclusion: It may be employed either alone or in combination with cryotherapy, existing chemotherapy, bypass surgery or radiations to achieve the optimal results in these patients. Nevertheless, there is a need to formulate a uniform dose and procedure to achieve homogeneity and develop references for clinical practices.

[ShRNA-mediated silencing of MDM2 inhibits growth of HepG2 hepatocellular carcinoma cells xenografted in nude mice].

OBJECTIVE: To construct a short hairpin (sh)RNA targeting the gene encoding the MDM2 oncoprotein in order to investigate its role in human hepatocellular carcinoma (HCC) and its potential for use as a gene therapy strategy to inhibit HCC growth in vivo. METHODS: Small interfering (si)RNAs were designed targeting the MDM2 gene (siMDM2-1 and siMDM2-2) and unrelated sequences (negative control) and cloned into the expression plasmid pGCSilencer-U6-neo-GFP. A HCC mouse model was established by subcutaneous inoculation of HepG2 cells (2 x 10(6) in 0.2 ml) into 20 nude mice. The inoculated mice were divided into four equal groups for tumor-localized injections of saline, negative control siRNA plasmid, siMDM2-1 plasmid, and siMDM2-2 plasmid. Tumor growth was observed daily (by caliper measurement) for one month, when mice were sacrificed by cervical dislocation. The tumor mass was resected for analysis of tumor inhibition rate (% = [(average tumor weight of control group - average tumor weight of treatment group) / average tumor weight of control group x 100]) and effects on MDM2 and p53 mRNA and protein expression (by reverse transcription- PCR and western blotting, both normalized to beta-actin). Significance of between-group differences was assessed by one-way ANOVA or LSD test; pairwise comparisons were made by the Chi-squared test. RESULTS: siMDM2-1 and siMDM2-2 suppressed the xenografted tumor growth remarkably (60.6% and 54.6% inhibition rates, respectively), significantly reduced the expression ofMDM2 gene (62.8% and 61.6%) and protein (60.7% and 59.5%), and significantly increased p53 gene (47.1% and 45.6%) and protein (45.9% and 44.3%) (all, P < 0.05). CONCLUSION: shRNA-mediated silencing of the MDM2 gene effectively inhibits HCC tumorigenesis of subcutaneously xenografted HepG2 cells in nude mice, and the mechanism may involve p53.