The role of mitochondrial dysfunction in macrophages on SiO2 -induced pulmonary fibrosis: A review.

Several epidemiologic and toxicological studies have widely regarded that mitochondrial dysfunction is a popular molecular event in the process of silicosis from different perspectives, but the details have not been systematically summarized yet. Thus, it is necessary to investigate how silica dust leads to pulmonary fibrosis by damaging the mitochondria of macrophages. In this review, we first introduce the molecular mechanisms that silica dust induce mitochondrial morphological and functional abnormalities and then introduce the main molecular mechanisms that silica-damaged mitochondria induce pulmonary fibrosis. Finally, we conclude that the mitochondrial abnormalities of alveolar macrophages caused by silica dust are involved deeply in the pathogenesis of silicosis through these two sequential mechanisms. Therefore, reducing the silica-damaged mitochondria will prevent the potential occurrence and fatality of the disease in the future.

The multifaceted role of macrophage mitophagy in SiO2-induced pulmonary fibrosis: A brief review.

Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2-induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2-induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2-induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy-inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2-induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

The role of macrophage-derived TGF-ß1 on SiO2-induced pulmonary fibrosis: A review.

Silicosis is an occupational fibrotic lung disease caused by inhaling large amounts of crystalline silica dust. Transforming growth factor-ß1 (TGF-ß1), which is secreted from macrophages, has an important role in the development of this disease. Macrophages can recognize and capture silicon dust, undergo M2 polarization, synthesize TGF-ß1 precursors, and secrete them out of the cell where they are activated. Activated TGF-ß1 induces cells from different sources, transforming them into myofibroblasts through autocrine and paracrine mechanisms, ultimately causing silicosis. These processes involve complex molecular events, which are not yet fully understood. This systematic summary may further elucidate the location and development of pulmonary fibrosis in the formation of silicosis. In this review, we discussed the proposed cellular and molecular mechanisms of production, secretion, activation of TGF-ß1, as well as the mechanisms through which TGF-ß1 induces cells from three different sources into myofibroblasts during the pathogenesis of silicosis. This study furthers the medical understanding of the pathogenesis and theoretical basis for diagnosing silicosis, thereby promoting silicosis prevention and treatment.

[Advanced glycated albumin induces macrophage pyroptosis via upregulating nucleotide-binding oligomerization domain-like receptor protein 3].

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on pyroptosis of macrophages and the underlying molecular mechanisms. RAW264.7 macrophages were treated with AGE-alb (1, 2, 4 and 6 g/L) and control albumin (C-alb, 4 g/L) for 24 h, or preincubated with MCC950 (1 µmol/L) for 1 h and then treated with AGE-alb (4 g/L) for 24 h. Cell viability and caspase-1 activity were measured by MTT and assay kits, respectively. Lactate dehydrogenase (LDH) activity and the levels of interleukin-1ß (IL-1ß) and IL-18 in media were detected. Cell death degree was evaluated by TUNEL and Hoechst 33342/PI staining. The protein levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), procaspase-1 and cleaved caspase-1 were assessed by Western blot. The results showed that AGE-alb treatment caused obvious decrease in cell viability and increases in LDH leakage and the percentages of TUNEL- or PI-positive cells in a concentration-dependent manner. Additionally, AGE-alb promoted IL-1ß and IL-18 secretion, upregulated NLRP3 expression, and increased caspase-1 activity especially at the dose of 4 and 6 g/L. However, MCC950 (an NLRP3 inhibitor) pretreatment inhibited significantly the decrease in cell viability and the increases in LDH leakage and percentages of TUNEL- or PI-positive cells induced by AGE-alb. Furthermore, MCC950 attenuated obviously AGE-alb-induced IL-1ß and IL-18 secretion and caspase-1 activation. These results indicate that AGE-alb may induce macrophage pyroptosis, and the mechanism is at least partially by activating NLRP3-caspase-1 pathway.

Location and dynamic changes of inflammation, fibrosis, and expression levels of related genes in SiO2-induced pulmonary fibrosis in rats in vivo.

Silicosis is a serious occupational disease characterized by pulmonary fibrosis, and its mechanism and progression have not been fully elucidated yet. In this study, silicosis models of rat were established by a one-time dusting method, and the rats were sacrificed after 30, 60, and 120 days (herein referred to as the 30, 60, and 120 days groups, respectively). The rats without dust exposure were used as the control. The lungs were removed to observe pathological changes using hematoxylin and eosin and Masson's trichrome staining and transmission electron microscopy, and the degree of collagen type I and III deposition in the lung was evaluated by enzyme-linked immunosorbent assay. The levels of malondialdehyde and superoxide dismutase were measured by spectrophotometry, and the expression levels of fibrosis-related genes (transforming growth factor beta 1, type I collagen, type III collagen) were assessed by real-time quantitative polymerase chain reaction. The results suggested that the rats in the model groups exhibited obvious collagen fibrosis and that the severity of the lung injury increased as the time after exposure to SiO2 increased. There was a significant response to lung inflammation in the model rats, especially in the 30 days group. The degree of lipid peroxidation in bronchoalveolar lavage fluid cells and lung tissues in experiment group rats significantly increased. Among the three fibrosis-related genes, transforming growth factor beta 1was elevated in both bronchoalveolar lavage fluid cells and lung tissues of the experiment group rats, while collagen type I and III were only elevated in lung tissues. Hence, we concluded that as silicosis progressed, inflammation, fibrosis, and the expression of fibrosis-related genes showed different time-dependent changes and that a number of causal relationships existed among them.

Performance of coralline hydroxyapatite in sinus floor augmentation: a retrospective study.

OBJECTIVE: The purpose of this study is to retrospectively explore the utilization of coralline hydroxyapatite in maxillary sinus augmentation. METHOD: One hundred and eighteen cases of sinus lift with coralline hydroxyapatite (CHA) were included in this study. In detail, simultaneous implantation was conducted in 78 patients (174 implants) and delayed implantation was done in 40 cases (82 implants) around 6 months after bone transplantation. The clinical features and X-ray radiographs after operation were analyzed to evaluate osseointegration procedures according to a planned medical follow-up. In the delayed group, around 6 months, a bone biopsy was taken just during implant placement in order to evaluate the new formed bone from a histological and histomorphometrical point of view. A further 6 months later, abutment connection was performed, and the patients received prosthetic restoration of the missing teeth. RESULT: Clinically, the incisions healed well. No abnormal reactions were found during follow-up period. All the 174 simultaneous implants were successful after 1-5 years of medical review; Out of 82 delayed implants, 3 were found to be loose. Histologically, all the specimens showed signs of active remodeling, and all the tissues had a large amount of osteocyte at sixth month after sinus augmentation. New bone formed dramatically. Radiologically, the density of CHA gradually reduced since the beginning of the third month, and CHA may be completely resolved at about fifth year. CONCLUSION: CHA is proven an ideal bone graft material for its reliable clinical results and favorable histocompatibility in the treatment of sinus atrophy or other kinds of insufficient bone volume in this region. Moreover, CHA's signal application can achieve desired clinical effect. CLINICAL RELEVANCE: This study shows the clinic application of CHA in maxillary sinus augmentation. Compared with popular mixture of autogenous bone and grafting materials, our results show CHA's signal application can achieve ideal osseointegration interface and satisfying clinic effect.

Molecular mechanism of the unusual biphasic effects of the natural compound hinokitiol on iron-induced cellular DNA damage.

Hinokitiol is a natural monoterpene compound found in the heartwood of cupressaceous plants that have anticancer and anti-inflammatory properties. However, few studies have focused on its effect on iron-mediated cellular DNA damage. Here we show that hinokitiol exhibited unusual biphasic effects on iron-induced DNA damage in a molar ratio (hinokitiol/iron) dependent manner in HeLa cells. Under low ratios (<3:1), hinokitiol markedly enhanced DNA damage induced by Fe(II) or Fe(II)-H2O2; However, when the ratios increased over 3:1, the DNA damage was progressively inhibited. We found that the total cytoplasmic and nuclear iron concentration increased as the ratios of hinokitiol/iron increased. However, the cellular level of labile iron pool (LIP) only increased at ratios lower than 3, and the ROS generation is consistent with LIP change. Hinokitiol was found to interact with iron to form lipophilic hinokitiol-iron complexes with different stoichiometry and redox-activity by complementary applications of various analytical methods. Taken together, we propose that the enhancement of iron-induced cellular DNA damage by hinokitiol at low ratios (<3:1) was due to formation of lipophilic and redox-active iron complexes which facilitated cellular iron uptake and •OH production, while the inhibition at ratios higher than 3 was due to formation of redox-inactive iron complexes. These new findings will help us to design more effective drugs for the prevention and treatment of a series of iron-related diseases via regulating the two critical physicochemical factors (lipophilicity and redox activity of iron complexes) by simple natural compounds with iron-chelating properties.

IL-7-Treated Periodontal Ligament Cells Regulate Local Immune Homeostasis by Modulating Treg/Th17 Cell Polarization.

Both interleukin (IL)-7 and human periodontal ligament cells (hPDLCs) have immunomodulatory properties. However, their combined effect on CD4+T cells has never been studied. In this study, we aimed to investigate the effect of conditioned medium of hPDLCs treated with rhIL-7 on the differentiation of CD4+T cells into regulatory T cells/T helper 17 cells (Treg/Th17 cells) and observe the effect of IL-7 on the immunomodulatory properties of PDLCs. After hPDLCs were treated with different concentrations of rhIL-7 for 24 h, the collected supernatants were used to incubate CD4+T cells for 3 days. A gamma-secretase inhibitor (DAPT) was used to suppress the activation of the Notch1 signaling pathway. Cell proliferation, apoptosis, and necrosis were determined using the cell counting kit-8 (CCK-8) and flow cytometry (FCM). The expressions of forkhead box P3 (Foxp3) in CD4+T cells and transforming growth factor (TGF-ß) and IL-6 in the supernatants were determined by ELISA. Reverse transcription-quantitative PCR (RT-qPCR), and the Western blot (WB) determined the mRNA levels and protein expression of various target factors. FCM was used to detect the mean fluorescence intensity of PD-L1 in hPDLCs and to analyze the differentiation of Treg/Th17 cells. Our results showed that IL-7 promoted proliferation and inhibited apoptosis in hPDLCs, promoted the expression of TGF-ß, PD-L1, Notch1, Jagged1, and Hes1, and inhibited the levels of hypoxia-inducible factor (HIF)-1α and TCF7, whereas the addition of DAPT effectively reversed these effects. Importantly, we found that the conditioned medium of hPDLCs treated with rhIL-7 promoted the polarization of CD4+T cells into Treg cells but had no significant effect on the differentiation of Th17 cells. Our study indicated that treatment of PDLCs with IL-7 can promote the polarization of CD4+T cells into Treg cells by modulating the expression of inflammatory factors and signaling molecules through activating the Notch1 signaling pathway, thus participating in the regulation of immune homeostasis in the periodontal microenvironment.

[Effects of exercise and nilestriol on bone size and bone mass in ovariectomized rats].

OBJECTIVE: To investigate the influence of nilestriol (CCE3) and exercise on bone size and bone mass in ovariectomized (OVX) rats. METHODS: Forty eight (48) female Sprague-Dawley (SD) rats were divided randomly into six groups: (1) Normal control group, (2) Sham OVX group, (3) OVX group, (4) OVX + CCE3 group, (5)) OVX + exercise group, (6) OVX + CCE3 + exercise group. CCE (0.5 mg/kg per week) was given to the rats in OVX + CCE3 group and OVX + CCE3 + exercise group from the 2nd day after the operation for 11 weeks. Exercise training was loaded to the rats in exercise groups from the 7th day after operation, each rat was subjected to running on 0 dig angle runway with the speed of 16 m per minute, 45 minutes per day, 5 days per week for 10 weeks. RESULTS: The bone diameter, bone volume, bone wet weight, bone dry weight, bone ashes weight in the OVX group were lower than those in the sham OVX group (P < 0.01). All of these measurements were increased in OVX + CCE3 group and OVX + exercise group when compared with the OVX group, but were still lower than those in sham OVX group (P < 0.01). Exercise enhances the effect of CCE3 (P < 0.01). CONCLUSION: Exercise enhances the effects of CCE3 on the improvement of both bone size and quantity in OVX rats.

Mechanism of synergistic DNA damage induced by caffeic acid phenethyl ester (CAPE) and Cu(II): Competitive binding between CAPE and DNA with Cu(II)/Cu(I).

Caffeic acid phenethyl ester (CAPE) is an active polyphenol of propolis from honeybee hives, and exhibits antioxidant and interesting pharmacological activities. However, in this study, we found that in the presence of Cu(II), CAPE exhibited pro-oxidative rather than antioxidant effect: synergistic DNA damage was induced by the combination of CAPE and Cu(II) together as measured by strand breakage in plasmid DNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, which is dependent on the molar ratio of CAPE:Cu(II). Production of Cu(I) and H2O2 from the redox reaction between CAPE and Cu(II), and subsequent OH formation was found to be responsible for the synergistic DNA damage. DNA sequencing investigations provided more direct evidence that CAPE/Cu(II) caused preferential cleavage at guanine, thymine and cytosine residues. Interestingly, we found there are competitive binding between CAPE and DNA with Cu(II)/Cu(I), which changed the redox activity of Cu(II)/Cu(I), via complementary applications of different analytical methods. The observed DNA damage was mainly attributed to the formation of DNA-Cu(II)/Cu(I) complexes, which is still redox active and initiated the redox reaction near the binding site between copper and DNA. Based on these data, we proposed that the synergistic DNA damage induced by CAPE/Cu(II) might be due to the competitive binding between CAPE and DNA with Cu, and site-specific production of OH near the binding site of copper with DNA. Our findings may have broad biological implications for future research on the pro-oxidative effects of phenolic compounds in the presence of transition metals.

[Effects of behind legs vibrations on erectile function in male rabbits].

OBJECTIVE: To study the effects of behind legs vibrations on erectile function in male rabbits through the concentration of plasma reproductive hormone and the expression of nitric oxide synthase (eNOS), endothelin-1 (ET-1) mRNA in vibrated male rabbits. METHODS: 30 male adult rabbits were assigned randomly to A group (vibration power: 3.02 m/s(2)), B group (vibration power: 6.13 m/s(2)), C group (vibration power: 12.26 m/s(2)) and control group. The concentration of expression of eNOS, ET-1 mRNA were measured with RT-PCR after rated for 30 days. RESULTS: (1) Compared with 0 days vibration, after exposure to vibration for 10, 20, 30 days, the A, B, C group concentration of plasma T, LH are much lower (P < 0.05), the concentration of plasma E2 is much higher. (2) Compared with control group after exposed for 30 days, the expression of ET-1 mRNA [B group:(17.39 +/- 4.59) x 104; C group: (36.21 +/- 13.13) x 104 ] were much higher and expression of eNOS mRNA [A group: (19.11 +/- 6.83) x 104; B group: (11.86 +/- 3.15) x 104; C group: (4.68 +/- 3.26) x 104] was much lower, there were significant differences (P < 0.01). CONCLUSIONS: The vibration of behind legs in rabbits resulted the concentration of plasma T, LH are much lower, the concentration of plasma E2 is much higher, increased the expression of eNOS mRNA, decreased the expression of eNOS mRNA, then vary the erectile function.

Effects of abnormal expression of fusion and fission genes on the morphology and function of lung macrophage mitochondria in SiO2-induced silicosis fibrosis in rats in vivo.

Silicosis is a serious occupational disease affecting millions of related workers. Many studies showed lung macrophages play an important role in the disease. However, the changes of macrophages are not fully characterized and the mechanisms need further investigations. The objectives of this work were to evaluate the effects of abnormal expression of fusion and fission genes on the morphology and function of lung macrophage mitochondria in SiO2-induced silicosis fibrosis in rats. In this study, the rats were injected with 1 mL of SiO2 suspension (100 mg/mL) into the lungs to establish silicosis models, and killed after 30, 60, and 120 days. The rats which were injected with normal saline (1 mL) into lungs were used as control. The lungs of rats were taken for pathological observation. Lung macrophages were collected to measure the number, activity, level of MDA and SOD, and relative content of fusion (Mfn1, Mfn2) and fission (Fis, DRP) genes. Subsequently, mitochondria were extracted from the macrophages to measure the changes of function, including MDA, SOD, ATP, and ATPase. We found that silica dust inhalation led to the proliferation of collagen fibers in the lung tissue. During this process, the number and activity of macrophages increased, the degree of lipid peroxidation increased, and the expression of mitochondrial fusion and fission genes was abnormal. Moreover, the mitochondrial lipid peroxidation level in macrophages increased, the production of ATP and the activity of ATPase decreased, and the abnormal forms of mitochondria occurred. Our results indicated that the morphology and function of mitochondria in macrophages changed during the progress of silicosis, which were related to the abnormal expression of fusion and fission genes.

Potential functions of long non­coding RNAs in the osteogenic differentiation of human bone marrow mesenchymal stem cells.

Long non­coding RNAs (lncRNAs) are a specific group of RNA molecules that do not encode proteins. They have been shown to serve important regulatory functions in various biological and cell differentiation processes. However, the potential functions and regulatory mechanisms of lncRNAs that are associated with the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) remain to be elucidated. The present study aimed to investigate lncRNAs that are differentially expressed during the osteogenic differentiation of hBMSCs, along with the potential functions of those lncRNAs. To this end, three groups of hBMSCs were stimulated to undergo osteogenic differentiation for 7 days. Known lncRNAs, unknown lncRNAs and mRNAs that demonstrated differential expression prior to and following the osteogenic differentiation of hBMSCs were screened using lncRNA high­throughput sequencing. In addition, 12 lncRNAs were selected for reverse transcription­quantitative polymerase chain reaction (RT­qPCR) validation of the accuracy of the sequencing results. The potential functions and possible targets of the differentially expressed lncRNAs were analyzed using bioinformatics technologies (gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene co­expression network analysis). In total, 64 lncRNAs were differentially expressed by at least two­fold in hBMSCs prior to and following osteogenic differentiation; these included seven known lncRNAs (two upregulated and five downregulated lncRNAs) and 57 unknown lncRNAs (35 upregulated and 22 downregulated lncRNAs). In addition, 409 mRNAs (257 upregulated and 152 downregulated mRNAs) were differentially expressed by at least two­fold. The RT­qPCR results obtained for 12 selected differentially expressed lncRNAs were consistent with the sequencing results. The gene co­expression network analysis of lncRNAs and mRNAs demonstrated that four lncRNAs (ENSG00000238042, lnc_1269, lnc_1369 and lnc_1708) may serve important roles in the osteogenic differentiation of hBMSCs. In conclusion, during the osteogenic differentiation of hBMSCs, the lncRNA expression profile changed significantly; certain of the observed differentially expressed lncRNAs may be derived from protein­coding genes and may serve important roles in osteogenic differentiation.

Association of toll-like receptors with the risk of oral squamous cell carcinoma.

AIM OF STUDY: Association of toll-like receptors (TLRs) with the risk of oral squamous cell carcinoma (OSCC) from the published reports is still conflicting. This study was conducted to evaluate the relationship between TLRs and the risk of OSCC using meta-analysis method. MATERIALS AND METHODS: The association studies were identified from PubMed and Cochrane Library on April 01 2015, and eligible investigations were included and synthesized using meta-analysis method. RESULT: Three reports were recruited into this meta-analysis for the association of TLRs with OSCC susceptibility. In this meta-analysis, we found that TLRs were not associated with OSCC susceptibility. However, in the sub-group analysis, we found that TLR-7 was associated with OSCC risk. CONCLUSION: TLR-7 was associated with OSCC risk. TLR-7 might be an indicator to predict the OSCC risk. However, more studies should be conducted to confirm it.

Surgery Combined with Radiotherapy Improved Survival in Metastatic Esophageal Cancer in a Surveillance Epidemiology and End Results Population-based Study.

This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC.

Impact of the number of resected lymph nodes on survival after preoperative radiotherapy for esophageal cancer.

To assess the impact of the number of resected lymph nodes (RLNs) for survival in esophageal cancer (EC) patients treated with preoperative radiotherapy and cancer-directed surgery. The Surveillance Epidemiology and End Results (SEER) database was queried to identify EC patients treated from 1988 to 2012 who had complete data on the number of positive lymph nodes and number of RLNs. Kaplan-Meier survival analysis and Cox regression proportional hazard methods were used to determine factors that significantly impact cause-specific survival (CSS) and overall survival (OS). There were a total of 3,159 patients who received preoperative radiotherapy and cancer-directed surgery. The median number of RLNs was 10 in both patients who received and did not receive preoperative radiotherapy (P = 0.332). Cox regression univariate and multivariate analysis showed that RLN count was a significant prognostic factor for CSS and OS. Patients with 11-71 RLNs had better CSS (hazard ratio [HR] = 0.694, 95% confidence interval [CI]: 0.603-0.799, P < 0.001) and OS (HR = 0.724, 95% CI: 0.636-0.824, P < 0.001) than patients with 1-10 RLNs. The 5-year CSS rates were 39.1% and 44.8% in patients with 1-10 RLNs and 11-71 RLNs, respectively (P < 0.001). The 5-year OS rates were 33.7% and 39.9% in patients with 1-10 RLNs and 11-71 RLNs, respectively (P < 0.001). A higher number of RLNs was associated with better survival by tumor stage and nodal stage (all P < 0.05). RLN count is an independent prognostic factor in EC patients who undergo preoperative radiotherapy and cancer-directed surgery.

Analysis of the mechanisms of rabbit's brainstem hemorrhage complicated with irritable changes in the alvine mucous membrane.

AIM: To explore the dynamic changes in the pressure of the lateral ventricle during acute brainstem hemorrhage and the changes of neural discharge of vagus nerve under the load of intracranial hypertension, so as to analyze their effects on the congestive degree of intestinal mucous membrane and the morphologic changes of intestinal mucous membrane. METHODS: An operation was made to open the skull to obtain an acute brainstem hemorrhage animal model. Microcirculatory microscope photography device and video recording system were used to determine the changes continuously in the caliber of jejunal mesenteric artery during brainstem hemorrhage and the changes with time in the congestion of jejunal mucosal villi. We used HE stain morphology to analyze the changes of duodenal mucosal villi. A recording electrode was used to calculate and measure the electric discharge activities of cervical vagus nerve. RESULTS: (1) We observed that the pressure of lateral cerebral ventricle increased transiently during acute brainstem hemorrhage; (2) The caliber of the jejunal mesenteric artery increased during brainstem hemorrhage. Analysis of red color coordinate values indicated transient increase in the congestion of jejunal mucous membrane during acute brainstem hemorrhage; (3) Through the analysis of the pathologic slice, we found enlarged blood vessels, stagnant blood, and transudatory red blood cells in the duodenal submucous layer; (4) Electric discharge of vagus nerve increased and sporadic hemorrhage spots occurred in duodenal mucous and submucous layer, when the lateral ventricle was under pressure. CONCLUSION: Brainstem hemorrhage could cause intracranial hypertension, which would increase the neural discharge of vagus nerve and cause the transient congestion of jejunal mucous membrane. It could cause hyperemia and diffused hemorrhage in the duodenal submucous layer 48 h after brainstem hemorrhage.

Clinical study on the treatment of chronic wound with negatively-charged aerosol.

BACKGROUND: Aerosols are defined as the mixture of liquid or solid particles/droplets that are stably suspending in air. When carrying a certain amount of negative charge, they will be defined as negatively-charged aerosol. This report investigates the effect of negatively-charged aerosol on the healing of chronic wound. METHODS: 140 patients with chronic wound were assigned randomly into two groups. Normal, routine treatment was applied on chronic wounds of 73 patients depending on wounds situation (control group). While another 67 similar patients received negatively-charged aerosol therapy (2 hours per time, twice a day) and were used as experimental group. Wound healing assessment including the patients' complication, detection of bacteria in wound secretions, and evaluation of wound healing. RESULTS: The results of our study showed that after the application of negatively-charged aerosols, and condition and infection rate of wounds from experiment group were better and lower than that of control group. In comparison with control group, the relative size of wounds from experiment group was significantly smaller (P<0.05) at post-treatment day 0, 7, 14, 21 and 28. Also, the time required for wound healing in the experimental group was significantly shorter (P<0.05) than that in the control group. CONCLUSION: Negatively-charged aerosol therapy can accelerate wound healing speed and improve the healing of chronic wounds. Thus, we wound recommend the consideration of Negatively-charged aerosol therapies in addition to normal wound treatment in cases of chronic wound.

In vitro and in vivo effect of 5-FC combined gene therapy with TNF-α and CD suicide gene on human laryngeal carcinoma cell line Hep-2.

This study was aimed to investigate the effect of combined cancer gene therapy with exogenous tumor necrosis factor-alpha (TNF-α) and cytosine deaminase (CD) suicide gene on laryngeal carcinoma cell line Hep-2 in vitro and in vivo. Transfection of the recombinant eukaryotic vectors of pcDNA3.1 (+) containing TNF-α and/or CD into Hep-2 cells resulted in expression of TNF-α and/or CD gene in vitro. The significant increase in apoptotic Hep-2 cells and decrease of Hep-2 cell proliferation were observed using 5-FC treatment combined with TNF-a expression by CD/5-FC suicide system. Moreover, bystander effect was also observed in the TNF-α and CD gene co-expression group. Laryngeal squamous cell carcinoma (LSCC) mice model was established by using BALB/c mice which different transfected Hep-2 cells with pcDNA3.1 (+) containing TNF-α and/or CD were applied subcutaneously. So these mice are divided into four groups, namely, (1)Hep-2/TIC group; (2)Hep-2/CD group; (3)Hep-2/TNF-α group; (4)Hep-2/0 group. At day 29 after cell inoculation, volume of grafted tumor had significant difference between each two of them (P<0.05). These results showed that the products of combined CD and TNF-α genes inhibited the growth of transplanted LSCC in mice model. So by our observed parameters and many others results, we hypothesized that 5-FC combined gene therapy with TNF-αand CD suicide gene should be an effective treatment on Laryngeal carcinoma.