A tetramethylpyrazine-loaded hyaluronic acid-based hydrogel modulates macrophage polarization for promoting wound recovery in diabetic mice.

The failure of wound healing often causes lower limb disability and amputation of diabetic patients. Current strategies for diabetic wound management often fail to achieve the expected outcomes, and emerging alternatives are urgently needed. Recent advances in the identification of active compounds from traditional herbal medicines provide promising therapeutics for tissue repair and regeneration. In this study, the pro-healing effects of tetramethylpyrazine (TMP, a natural alkaloid found in Ligusticum chuanxiong Hort) for diabetic wounds were for the first time demonstrated. The cutaneous healing was mainly achieved by TMP-mediated macrophage polarization from pro-inflammatory to pro-healing phenotype. In addition, the topical administration of TMP was facilitated by the hyaluronic acid (HA) hydrogel for promoting the full-thickness wounds in the experimental diabetic mice. Consequently, TMP-loaded HA hydrogel (TMP-HA) profoundly accelerated the wound closure in comparison with TMP-loaded INTRASITE Gel (it is a commercial hydrogel), which was evident with the inflammation mitigation, the angiogenesis enhancement, and the collagen deposition. Our work reveals the macrophage-modulatory function of TMP for diabetic wound healing and demonstrates great potential of TMP-HA for clinical application.

Nano co-delivery of Plumbagin and Dihydrotanshinone I reverses immunosuppressive TME of liver cancer.

Hepatocellular carcinoma (HCC) is resistant to current immunotherapy. This poor outcome mainly results from the immunosuppressive characteristics of tumor microenvironment (TME). Accumulating evidence indicates that some chemotherapy agents trigger immunogenic cell death (ICD), providing a promising strategy to remodel the immunosuppressive TME. The role of Plumbagin (PLB, a naphthoquinone compound from Plumbago zeylanica L.) as the ICD inducer for HCC cells was confirmed in this study. Dihydrotanshinone I (DIH, a phenanthraquinone compound of Salvia miltiorrhiza) functioned as the ICD enhancer by generating the reactive oxygen species (ROS). A poly(D,L-lactic-co-glycolic acid) (PLGA)-based nanoparticle (NP) was used to co-encapsulate PLB, DIH and NH4HCO3 (a pH sensitive adjuvant). This NP was further coated with the mannose-inserted erythrocyte membrane to produce a nanoformulation. This nanoformulation significantly increased the half-life and tumor targeting of two drugs in orthotopic HCC mice, generating chemo-immunotherapeutic effects for reversal of immunosuppressive TME. Consequently, the biomimetic nanoformulation loaded with low doses of PLB and DIH achieved significantly longer survival of HCC mice, without causing toxic signs. Our study demonstrates a promising strategy for remodeling the immunosuppressive TME of liver cancer.

A cyclodextrin-based nanoformulation achieves co-delivery of ginsenoside Rg3 and quercetin for chemo-immunotherapy in colorectal cancer.

The immune checkpoint blockade therapy has profoundly revolutionized the field of cancer immunotherapy. However, despite great promise for a variety of cancers, the efficacy of immune checkpoint inhibitors is still low in colorectal cancer (CRC). This is mainly due to the immunosuppressive feature of the tumor microenvironment (TME). Emerging evidence reveals that certain chemotherapeutic drugs induce immunogenic cell death (ICD), demonstrating great potential for remodeling the immunosuppressive TME. In this study, the potential of ginsenoside Rg3 (Rg3) as an ICD inducer against CRC cells was confirmed using in vitro and in vivo experimental approaches. The ICD efficacy of Rg3 could be significantly enhanced by quercetin (QTN) that elicited reactive oxygen species (ROS). To ameliorate in vivo delivery barriers associated with chemotherapeutic drugs, a folate (FA)-targeted polyethylene glycol (PEG)-modified amphiphilic cyclodextrin nanoparticle (NP) was developed for co-encapsulation of Rg3 and QTN. The resultant nanoformulation (CD-PEG-FA.Rg3.QTN) significantly prolonged blood circulation and enhanced tumor targeting in an orthotopic CRC mouse model, resulting in the conversion of immunosuppressive TME. Furthermore, the CD-PEG-FA.Rg3.QTN achieved significantly longer survival of animals in combination with Anti-PD-L1. The study provides a promising strategy for the treatment of CRC.

Modulation of macrophages by a paeoniflorin-loaded hyaluronic acid-based hydrogel promotes diabetic wound healing.

The impaired wound healing in diabetes is a central concern of healthcare worldwide. However, current treatments often fail due to the complexity of diabetic wounds, and thus, emerging therapeutic approaches are needed. Macrophages, a prominent immune cell in the wound, play key roles in tissue repair and regeneration. Recent evidence has demonstrated that macrophages in diabetic wounds maintain a persistent proinflammatory phenotype that causes the failure of healing. Therefore, modulation of macrophages provides great promise for wound healing in diabetic patients. In this study, the potential of paeoniflorin (PF, a chemical compound derived from the herb Paeonia lactiflora) for the transition of macrophages from M1 (proinflammatory phenotype) to M2 (anti-inflammatory/prohealing phenotype) was confirmed using ex vivo and in vivo experimental approaches. A hydrogel based on high molecular weight hyaluronic acid (HA) was developed for local administration of PF in experimental diabetic mice with a full-thickness wound. The resultant formulation (HA-PF) was able to significantly promote cutaneous healing as compared to INTRASITE Gel (a commercial hydrogel wound dressing). This outcome was accompanied by the amelioration of inflammation, the improvement of angiogenesis, and re-epithelialization, and the deposition of collagen. Our study indicates the significant potential of HA-PF for clinical translation in diabetic wound healing.

A folate-targeted PEGylated cyclodextrin-based nanoformulation achieves co-delivery of docetaxel and siRNA for colorectal cancer.

Docetaxel (DTX) is a chemotherapeutic agent used for a range of cancers, but it has little activity against colorectal cancer (CRC). However, combination therapy with other therapeutic agents is a potential strategy to enhance the efficacy of DTX in CRC treatment. The nuclear factor-κB (NF-κB) signaling pathway is implicated in a variety of malignancies (e.g., CRC), and the blockade of NF-κB may increase the sensitivity of cancer cells to chemotherapy. The application of small interference RNA (siRNA) to inhibit the translation of complementary mRNA has demonstrated the potential for cancer gene therapy. In this study, an amphiphilic cationic cyclodextrin (CD) nanoparticle modified with PEGylated folate (FA; a ligand to target folate receptor on CRC) has been developed for co-delivery of DTX and siRNA (against the RelA, a subunit of NF-κB) in the treatment of CRC. The resultant co-formulation (CD.DTX.siRelA.PEG-FA) achieved cell-specific uptake indicating the function of the folate targeting ligand. The CD.DTX.siRelA.PEG-FA nanoparticle enhanced the apoptotic effect of DTX with the downregulation of RelA expression, which significantly retarded the growth of CRC in mice, without causing significant toxicity. These results suggest that the FA-targeted PEGylated CD-based co-formulation provides a promising strategy for combining DTX and siRNA in treating CRC.

Synergism of rMV-Hu191 with cisplatin to treat gastric cancer by acid sphingomyelinase-mediated apoptosis requiring integrity of lipid raft microdomains.

BACKGROUND: DDP-based chemotherapy is one of the first-line treatment in GC. However, the therapeutic efficacy of DDP is limited due to side effects. Therefore, it is of great significance to develop novel adjuvants to synergize with DDP. We had demonstrated previously that rMV-Hu191 had antitumor activity in GC. Here we examined the synergism of rMV-Hu191 with DDP in vitro and in vivo. METHODS: Cellular proliferation, the synergistic effect and cell apoptosis were evaluated by CCK-8 assay, ZIP analysis and flow cytometry, respectively. The protein levels and location of ASMase were monitored by western blot and immunofluorescence assay. shRNA and imipramine were used to regulate the expression and activity of ASMase. MßCD was administrated to disrupt lipid rafts. Mice bearing GC xenografts were used to confirm the synergism in vivo. RESULTS: From our data, combinational therapy demonstrated synergistic cytotoxicity both in resistant GC cell lines from a Chinese patient and drug-nonresistant GC cell lines, and increased cell apoptosis, instead of viral replication. Integrity of lipid rafts and ASMase were required for rMV-Hu191- and combination-induced apoptosis. The ASMase was delivered to the lipid raft microdomains at the initial stage of rMV-Hu191 treatment. In vivo GC mice xenografts confirmed the synergism of combinational treatment, together with increased apoptosis and trivial side-effects. CONCLUSIONS: This is the first study to demonstrate that rMV-Hu191 combined with DDP could be used as a potential therapeutic strategy in GC treatment and the ASMase and the integrity of lipid rafts are required for the synergistic effects.

A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway.

The potential therapeutic effects of oncolytic measles virotherapy have been verified against plenty of malignancies. However, the oncolytic effects and underlying mechanisms of the recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191) against human colorectal cancer (CRC) remain elusive. In this study, the antitumor effects of rMV-Hu191 were evaluated in CRC both in vitro and in vivo. From our data, rMV-Hu191 induced remarkably caspase-dependent apoptosis and complete autophagy in vitro. In mice bearing CRC xenografts, tumor volume was remarkably suppressed and median survival was prolonged significantly with intratumoral treatment of rMV-Hu191. To gain further insight into the relationship of rMV-Hu191-induced apoptosis and autophagy, we utilized Rapa and shATG7 to regulate autophagy. Our data suggested that autophagy was served as a protective role in rMV-Hu191-induced apoptosis in CRC. PI3K/AKT signaling pathway as one of the common upstream pathways of apoptosis and autophagy was activated in CRC after treatment with rMV-Hu191. And inhibition of PI3K/AKT pathway using LY294002 was accompanied by enhanced apoptosis and decreased autophagy which suggested that PI3K/AKT pathway promoted rMV-Hu191-induced autophagy and inhibited rMV-Hu191-induced apoptosis. This is the first study to demonstrate that rMV-Hu191 could be used as a potentially effective therapeutic agent in CRC treatment. As part of the underlying cellular mechanisms, apoptosis and autophagy were involved in the oncolytic effects generated by rMV-Hu191. And the cross-talk between these two processes and the PI3K/AKT signaling pathway was well identified.

Establishment of an efficient reverse genetic system of Mumps virus S79 from cloned DNA.

BACKGROUND: Mumps is a common type of respiratory infectious disease caused by mumps virus (MuV), and can be effectively prevented by vaccination. In this study, a reverse genetic system of MuV that can facilitate the rational design of safer, more efficient mumps vaccine candidates is established. METHODS: MuV-S79 cDNA clone was assembled into a full-length plasmid by means of the GeneArt™ High-Order Genetic Assembly System, and was rescued via reverse genetic technology. RT-PCR, sequencing, and immunofluorescence assays were used for rMuV-S79 authentication. Viral replication kinetics and in vivo experimental models were used to evaluate the replication, safety, and immunogenicity of rMuV-S79. RESULTS: A full-length cDNA clone of MuV-S79 in the assembly process was generated by a novel plasmid assemble strategy, and a robust reverse genetic system of MuV-S79 was successfully established. The established rMuV-S79 strain could reach a high virus titer in vitro. The average viral titer of rMuV-S79 in the lung tissues was 2.68 ± 0.14 log10PFU/g lung tissue, and rMuV-S79 group did not induce inflammation in the lung tissues in cotton rats. Neutralizing antibody titers induced by rMuV-S79 were high, long-lasting and could provide complete protection against MuV wild strain challenge. CONCLUSION: We have established a robust reverse genetic system of MuV-S79 which can facilitate the optimization of mumps vaccines. rMuV-S79 rescued could reach a high virus titer and the safety was proven in vivo. It could also provide complete protection against MuV wild strain challenge.

Attenuated MuV-S79 as vector stably expressing foreign gene.

BACKGROUND: To describe mumps virus (MuV) used as a vector to express enhanced green fluorescent protein (EGFP) or red fluorescent protein (RFP) genes. METHODS: Molecular cloning technique was applied to establish the cDNA clones of recombinant mumps viruses (rMuVs). rMuVs were recovered based on our reverse genetic system of MuV-S79. The properties of rMuVs were determined by growth curve, plaque assay, fluorescent microscopy and determination of fluorescent intensity. RESULTS: Three recombinant viruses replicated well in Vero cells and similarly as parental rMuV-S79, expressed heterologous genes in high levels, and were genetically stable in at least 15 passages. CONCLUSION: rMuV-S79 is a promising platform to accommodate foreign genes like marker genes, other antigens and immunomodulators for addressing various diseases.

A recombinant measles virus vaccine strain rMV-Hu191 has oncolytic effect against human gastric cancer by inducing apoptotic cell death requiring integrity of lipid raft microdomains.

Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.

Spatiotemporal epidemiology of, and factors associated with, the tuberculosis prevalence in northern China, 2010-2014.

BACKGROUND: Tuberculosis (TB) is an important public health issue worldwide. However, evidence concerning the impact of environmental factors on TB is sparse. We performed a retrospective analysis to determine the spatiotemporal trends and geographic variations of, and the factors associated with, the TB prevalence in Inner Mongolia. METHODS: We performed a retrospective analysis of the epidemiology of TB. A Bayesian spatiotemporal model was used to investigate the spatiotemporal distribution and trends of the TB prevalence. A spatial panel data model was used to identify factors associated with the TB prevalence in the 101 counties of Inner Mongolia, using county-level aggregated data collected by the Inner Mongolia Center for Disease Control and Prevention. RESULTS: From January 2010 to December 2014, 79,466 (6.36‱) incident TB cases were recorded. The TB prevalence ranged from 4.97‱ (12,515/25,167,547) in 2014 to 7.49‱ (18,406/ 24,578,678) in 2010; the majority of TB cases were in males, and in those aged 46-60 years; by occupation, farmers and herdsmen were the most frequently affected. The Bayesian spatiotemporal model showed that the overall TB prevalence decreased linearly from 2010 to 2014 and occupation-stratified analyses yielded similar results, corroborating the reliability of the findings. The decrease of TB prevalence in the central-western and eastern regions was more rapid than that in the overall TB prevalence. A spatial correlation analysis showed spatial clustering of the TB prevalence from 2011 to 2014 (Moran's index > 0, P < 0.05); in the spatial panel data model, rural residence, birth rate, number of beds, population density, precipitation, air pressure, and sunshine duration were associated with the TB prevalence. CONCLUSIONS: The overall TB prevalence in Inner Mongolia decreased from 2010 to 2014; however, the incidence of TB was high throughout this period. The TB prevalence was influenced by a spatiotemporal interaction effect and was associated with epidemiological, healthcare, and environmental factors.

[LKB1 regulates epithelial-mesenchymal transition in Peutz-Jeghers hamartoma and intestinal epithelial cells].

OBJECTIVE: To investigate the molecular mechanism by which LKB1 regulates epithelial-mesenchymal transition (EMT) in Peutz-Jeghers hamartoma and intestinal epithelial cells. METHODS: Immunohistochemistry was used to detect gene expression of LKB1, E-cadherin, and vimentin in 20 hamartoma tissues and 10 normal intestinal tissues, and collagen fiber deposition was analyzed using Masson trichrome staining. Normal intestinal epithelial NCM460 cells were transfected with LKB1 shRNA plasmid or negative control via lentiviral vectors, and the role of LKB1 in cell polarization and migration were determined using CCK8 and Transwell assays. Western blotting, quantitative real-time PCR (qPCR) and immunofluorescence were used to assess the alterations of EMT markers in the cells with LKB1 knockdown. RESULTS: Compared with normal intestinal tissues, hamartoma polyps showed significantly decreased LKB1 and E-cadherin expressions and increased vimentin expression with increased collagen fiber deposition. The cells with LKB1 knockdown exhibited enhanced cell proliferation and migration activities (P<0.01). Western blot analysis, qPCR and immunofluorescence all detected decreased E-cadherin and increased N-cadherin, vimentin, Snail, and Slug expressions in the cells with LKB1 knockdown. CONCLUSION: s LKB1 deficiency triggers EMT in intestinal epithelial cells and Peutz-Jeghers hamartoma, suggesting that EMT can serve as the therapeutic target for treatment of Peutz-Jeghers syndrome.

Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.

Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab')2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab')2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.

Training in early gastric cancer diagnosis improves the detection rate of early gastric cancer: an observational study in China.

Few studies have analyzed the training of endoscopists in the diagnosis of early gastric cancer (EGC). This study assessed whether specific training of endoscopists improves the detection rate of EGC. The rates of detection of EGC by endoscopists at the Digestive Endoscopy Center of the Affiliated Nanfang Hospital of China Southern Medical University between January 2013 and May 2014 were retrospectively analyzed. Because some endoscopists received training in the diagnosis of EGC, beginning in September 2013, the study was divided into 3 time periods: January to September 2013 (period 1), September 2013 to January 2014 (period 2), and January to May 2014 (period 3). The rates of EGC detection during these 3 periods were analyzed. From January 2013 to May 2014, a total of 25,314 gastroscopy examinations were performed at our center, with 48 of these examinations (0.2%) detecting EGCs, accounting for 12.1% (48/396) of the total number of gastric cancers detected. The EGC detection rates by trained endoscopists during periods 1, 2, and 3 were 0.3%, 0.6%, and 1.5%, respectively, accounting for 22.0%, 39.0%, and 60.0%, respectively, of the gastric cancers detected during these time periods. In comparison, the EGC detection rates by untrained endoscopists during periods 1, 2, and 3 were 0.05%, 0.08%, and 0.10%, respectively, accounting for 3.1%, 6.0%, and 5.7%, respectively, of the gastric cancers detected during these times. After training, the detection rate by some trained endoscopists markedly increased from 0.2% during period 1 to 2.3% during period 3. Further, the use of magnifying endoscopy with narrow-band imaging (M-NBI) (odds ratio = 3.1, 95% confidence interval 2.4-4.1, P < 0.001) contributed to the diagnosis of EGC. In conclusion, specific training could improve the endoscopic detection rate of EGC. M-NBI contributed to the diagnosis of EGC.

Experience with the second-generation Wallis interspinous dynamic stabilization device implanted in degenerative lumbar disease: a case series of 50 patients.

AIM: This study aimed to evaluate the short- to medium-term outcomes of the second-generation Wallis interspinous dynamic stabilization device for treatment of lumbar degenerative disease. MATERIAL AND METHODS: Fifty patients with lumbar degenerative disease treated from August 2007 to September 2009 were included in this retrospective study. The Japanese Orthopedic Association (JOA) score and the Oswestry Disability Index (ODI) were used for therapeutic efficacy evaluation. Odom's criteria were used to evaluate postoperative outcome with regard to symptoms. Anteroposterior X-rays were obtained after surgery. All patients were followed up for 2 years. RESULTS: Based on Odom's criteria, 22, 24 and 4 patients had excellent, good, and fair results respectively. The JOA score at 3, 12, and 24 months after surgery was significantly higher than before surgery (all p < 0.001), and the ODI score at 3, 12, and 24 months after surgery was significantly lower than before surgery (all p < 0.001). The posterior intervertebral disc height and the neural foramina height at 12 and 24 months after surgery was significantly higher than before surgery (both p < 0.001). CONCLUSION: Implantation of the second-generation Wallis interspinous dynamic stabilization device produced satisfactory clinical outcome at short- and medium-term follow-up in patients with lumbar degenerative disease.

[Unilateral pedicle screw fixation and transforaminal lumbar interbody fusion through paraspinal muscle approach for recurrent lumbar disc herniation combined with lumbar instability].

OBJECTIVE: To explore the clinical effects of unilateral pedicle screw fixation and transforaminal lumbar interbody fusion (TLIF) through paraspinal muscle approach for recurrent lumbar disc herniation combined with lumbar instability. METHODS: A total of 35 patients with recurrent lumbar disc herniation combined with lumbar instability were treated between March 2008 and May 2010, including 15 patients managed by the paraspinal muscle approach with unilateral pedicle screw fixation and transforaminal lumbar interbody fusion (TLIF) (unilateral fixation group) and 20 patients by the posterior midline approach with bilateral pedicle screw fixation and posterior lumbar interbody fusion (bilateral fixation group). Operation time and intraoperative blood loss were observed, preoperative and postoperative JOA score and VAS score in low back pain and legs pain, the interbody fusion condition were compared between two groups. RESULTS: All patients were followed up from 6 to 30 months with an average 16.8 months. All clinical symptoms had obviously improved postoperatively. X-rays showed good interbody fusion (only 1 case did not obtain fusion in bilateral fixation group) without cage displacement or settlement and implant loosening or breakage. There was significant difference in operation time and the intraoperative blood loss between two groups (P < 0.05). Postoperative JOA score had obviously decreased than preoperative one (P < 0.05). At 1 week after surgery, there was significant difference in VAS score of low back pain between two groups and there was no significant difference in VAS score of legs pain between two groups (P > 0.05); at final follow-up, there was no significant difference in VAS score of low back pain and legs pain between two groups (P > 0.05). CONCLUSION: Two methods both can obtain satisfactory effect in treating recurrent lumbar disc herniation combined with lumbar instability. Through the paraspinal muscle approach with unilateral pedicle screw fixation and TLIF has advantages of smaller surgical incision, shorter operation time, less intraoperative blood loss, faster relief in low back pain after operation, etc.

Low molecular weight heparin relieves experimental colitis in mice by downregulating IL-1ß and inhibiting syndecan-1 shedding in the intestinal mucosa.

Low molecular weight heparin (LMWH) exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS)-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18). Disease activity was scored by a disease activity index (DAI). Histological changes were evaluated by hematoxylin and eosin (HE) staining. The mRNA levels of syndecan-1, interleukin (IL)-1ß, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group). In addition, LMWH significantly decreased the expression of both IL-1ß and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group). LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa.

[Clinical analysis of an interspinous stabilization system (wallis) in treating lumbar degenerative disease].

OBJECTIVE: To evaluate clinical results of an interspinous stabilization system (Wallis) in treating lumbar degenerative disease in the short-term. METHODS: From August 2007 to June 2010,48 patients with lumbar degenerative disease who were treated with interspinous stabilization system, the data of patients were analyzed retrospectively. In all of the 48 cases, there were 30 males and 18 females with an average age of 54.2 years (ranged, 40 to 68 years). Forty-four cases were with single segment and 4 cases with two segments. Of them, 4 cases were in L3, 4, 40 cases were in L4, 5, 4 cases were in L3, 4 and L4, 5. The radiographic data of patients were analyzed. Clinical effects were evaluated by Japanese Orthopedic Association (JOA) score system and low back pain disability questionnaire (Oswestry) and Odom method. RESULTS: All the patients were followed up from 1 to 2 years with an average of 18 months. According to Odom's criteria, 20 cases obtained excellent results, 24 good, 4 fair. JOA score increased from 12.4 +/- 2.7 preoperatively to 26.1 +/- 2.0 postoperatively (P < 0.01). Oswestry score decreased from 14.1 +/- 2.9 preoperatively to 5.5 +/- 1.8 postoperatively (P < 0.01). The posterior height of intervertebral space and height of nerve root canal increased compared with that of preperative height. CONCLUSION: The treatment of lumbar degenerative disease with interspinous stabilization system can obtain satisfactory effects in the near future. It can retain dynamic stable of corresponding segments, expand volume of vertebral canal, and is safe and feasible.

[Changes in the biological behaviors of colon cancer cells under simulated hypoxia in vitro].

OBJECTIVE: To investigate the reactivity of colon cancer cell line SW480 and CD133(+) SW480 subsets to hypoxia in vitro and the changes in the expressions of anti-apoptosis and angiogenesis genes. METHODS: SW480 cells was subjected to CoCl(2) exposure at varying concentrations and for different time lengths to induce hypoxia, and the protein expression of hypoxia induced factor 1α (HIF-1α) was detected by Western blotting. The CD133(+) SW480 cells were sorted by magnetic activated cell sorting (MACS) and their proportion was assayed by flow cytometry (FCM). The CD133(+) SW480 subsets were exposed to CoCl(2) at the optimal concentration with exposure time selected in terms of HIF-1α level, and their tumor stem cell sphere formation ability was evaluated. Real-time PCR was used to compare the mRNA expression levels of the surface markers of colon cancer stem cells (CD133 and PROM1), survivin, and vascular endothelial growth factor (VEGF). RESULTS: Exposure to 200 µmol/L CoCl(2) for 8 h resulted in the highest HIF-1α expression in SW480 cells, but the same exposure failed to induce HIF-1α expression in CD133(+) SW480 subsets. The CD133(+) SW480 subsets, after CoCl(2)-induced hypoxia, showed significantly enhanced ability of cell sphere formation. Hypoxia of SW480 cells caused significant increases in CD133, survivin and VEGF mRNA levels by 1.607∓0.103, 2.745∓0.370 and 3.798∓0.091 folds, respectively (P<0.05). CONCLUSION: CoCl(2) can simulate hypoxia in colon cancer cells in vitro to induce stable HIF-1α expression, which is concentration- and time-dependent. The hypoxia-stimulated tumor stem sells show an enhanced sphere formation and anti-apoptotic and anti-angiogenic abilities.

[Sample targeting under stereomicroscopy can raise the detection rate of early colorectal cancer].

OBJECTIVE: To establish a set of pathological diagnosis method to raise the detection rate of early colorectal cancer. METHODS: All patients with colorectal tumor underwent ordinary electron enteroscopy in 2005. The lesions larger than 10 mm underwent indigo carmine staining and magnifying electron enteroscopy to observe the pit pattern. Endoscopic mucosal resection (EMR) or endoscopic piecemeal resection (EPMR) was performed on the suspected cases of cancer, such as laterally spreading tumor (LST). The resected specimens were stained with cresyl violet and observed by stereomicroscopy to determine the pit patterns. The parts showing the pit patterns associated with early colorectal cancer were targeted and biopsy specimens collected here to undergo pathohistological examination. Routine pathological examination was conducted on the other parts of the same specimen as control. The results of these specimens were compared with those of the specimens collected by ordinary methods from the patients with colorectal tumor in 2004. RESULTS: In 2005 40 patients with colorectal tumor were suspected as with cancer and underwent EMR or EPMR of which 16 were confirmed to be with early stage colorectal cancer, including severe dysplasia by sampling targeting (40%). And the routine pathohistological examination of the randomly collected parts from these same specimens showed 15 cases of mild or moderate dysplasia and only one case of severe dysplasia, with a detection rate of 2.5%, significantly lower than that of the result of sample targeting under stereomicroscopy (P < 0.01). In 2004, out of the 54 patients suspected to be with colorectal cancer only 4 cases of early cancer, including severe dysplasia were detected with a detection rate of 7.4%, significantly than that of the year 2005 (P < 0.01). CONCLUSION: Sample targeting and localized biopsy under stereomicroscopy raises the detection rate of early colorectal cancer.