Endogenous hydrogen sulfide inhibition suppresses tumor growth by promoting apoptosis and pyroptosis in esophageal cancer cells.

BACKGROUND: Hydrogen sulfide (H2S) has been identified as the third gaseous signaling molecule. Endogenous H2S plays a key role in the progression of various types of cancer. However, the effect of endogenous H2S on the growth of esophageal cancer (EC) remains unknown. METHODS: In this study, three kinds of H2S-producing enzymes inhibitors, DL-propargylglycine (PAG, inhibitor of cystathionine-γ-lyase), aminooxyacetic acid (AOAA, inhibitor of cystathionine-ß-synthase), and L-aspartic acid (L-Asp, inhibitor of 3-mercaptopyruvate sulfurtransferase) were used to determine the role of endogenous H2S in the growth of EC9706 and K450 human EC cells. RESULTS: The results indicated that the combination (PAG+AOAA+L-Asp) group showed higher inhibitory effects on the viability, proliferation, migration, and invasion of EC cells than PAG, AOAA, and L-Asp group. Inhibition of endogenous H2S promoted apoptosis via activation of mitogen-activated protein kinase pathway in EC cells. Endogenous H2S suppression triggered pyroptosis of EC cells by activating reactive oxygen species-mediated nuclear factor-κB signaling pathway. In addition, the combine group showed its more powerful growth-inhibitory effect on the growth of human EC xenograft tumors in nude mice without obvious toxicity. CONCLUSION: Our results indicate that inhibition of endogenous H2S production can significantly inhibit human EC cell growth via promotion of apoptosis and pyroptosis. Endogenous H2S may be a promising therapeutic target in EC cells. Novel inhibitors for H2S-producing enzymes can be designed and developed for EC treatment.

Inhibition of endogenous hydrogen sulfide production suppresses the growth of nasopharyngeal carcinoma cells.

Hydrogen sulfide (H2 S) has been widely recognized as one of gasotransmitters. Endogenous H2 S plays a crucial role in the progression of cancer. However, the effect of endogenous H2 S on the development of nasopharyngeal carcinoma (NPC) is still unknown. In this study, aminooxyacetic acid (AOAA, an inhibitor of cystathionine-ß-synthase), dl-propargylglycine (PAG, an inhibitor of cystathionine-γ-lyase), and l-aspartic acid (l-Asp, an inhibitor of 3-mercaptopyruvate sulfurtransferase) were adopted to detect the role of endogenous H2 S in NPC growth. The results indicated that the combine (PAG + AOAA + l-Asp) group had higher inhibitory effect on the growth of NPC cells than the PAG, AOAA, and l-Asp groups. There were similar trends in the levels of apoptosis and reactive oxygen species (ROS). In addition, the combine group exhibited lower levels of phospho (p)-extracellular signal-regulated protein kinase but higher expressions of p-p38 and p-c-Jun N-terminal kinase than those in the AOAA, PAG, and l-Asp groups. Furthermore, the combine group exerted more potent inhibitory effect on NPC xenograft tumor growth without obvious toxicity. In summary, suppression of endogenous H2 S generation could dramatically inhibit NPC growth via the ROS/mitogen-activated protein kinase pathway. Endogenous H2 S may be a novel therapeutic target in human NPC cells. Effective inhibitors for H2 S-producing enzymes could be designed and developed for NPC treatment.

Role of hydrogen sulphide in physiological and pathological angiogenesis.

The role of hydrogen sulphide (H2 S) in angiogenesis has been widely demonstrated. Vascular endothelial growth factor (VEGF) plays an important role in H2 S-induced angiogenesis. H2 S promotes angiogenesis by upregulating VEGF via pro-angiogenic signal transduction. The involved signalling pathways include the mitogen-activated protein kinase pathway, phosphoinositide-3 kinase pathway, nitric oxide (NO) synthase/NO pathway, signal transducer and activator of transcription 3 (STAT3) pathway, and adenosine triphosphate (ATP)-sensitive potassium (KATP ) channels. H2 S has been shown to contribute to tumour angiogenesis, diabetic wound healing, angiogenesis in cardiac and cerebral ischaemic tissues, and physiological angiogenesis during the menstrual cycle and pregnancy. Furthermore, H2 S can exert an anti-angiogenic effect by inactivating Wnt/ß-catenin signalling or blocking the STAT3 pathway in tumours. Therefore, H2 S plays a double-edged sword role in the process of angiogenesis. The regulation of H2 S production is a promising therapeutic approach for angiogenesis-associated diseases. Novel H2 S donors and/or inhibitors can be developed in the treatment of angiogenesis-dependent diseases.

Cystathionine ß-Synthase Regulates the Proliferation, Migration, and Invasion of Thyroid Carcinoma Cells.

Thyroid cancer is considered to be one of the most common endocrine tumors worldwide. Cystathionine ß-synthase (CBS) plays a crucial role in the occurrence of several types of malignancies. And yet, the mechanism of action of CBS in the growth of thyroid carcinoma cells is still unrevealed. We found that CBS level in thyroid carcinoma tissue was higher than that in adjacent normal tissue. The overexpression of CBS enhanced the proliferation, migration, and invasion of thyroid cancer cells, while the downregulation of CBS exerted reverse effects. CBS overexpression reduced the levels of cleaved caspase-3 and cleaved poly ADP-ribose polymerase in thyroid cancer cells, whereas CBS knockdown showed reverse trends. CBS overexpression decreased reactive oxygen species (ROS) levels but increased the levels of Wnt3a and phosphorylations of phosphatidylinositol 3-kinase (PI3K), protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR), ß-catenin, and glycogen synthase kinase-3 beta, while CBS knockdown exerted opposite effects. In addition, CBS overexpression promoted the growth of xenografted thyroid carcinoma, whereas CBS knockdown decreased the tumor growth by modulating angiogenesis, cell cycle, and apoptosis. Furthermore, aminooxyacetic acid (an inhibitor of CBS) dose-dependently inhibited thyroid carcinoma cell growth. CBS can regulate the proliferation, migration, and invasion of human thyroid cancer cells via ROS-mediated PI3K/AKT/mTOR and Wnt/ß-catenin pathways. CBS can be a potential biomarker for diagnosing or prognosing thyroid carcinoma. Novel donors that inhibit the expression of CBS can be developed in the treatment of thyroid carcinoma.

The Effects of the Application of the "One Disease, One Product" Program to Nursing Practice for Patients After the Resection of Pituitary Adenomas Using the Endonasal Transsphenoi.

OBJECTIVE: To explore the application and effect of the "one disease, one product" project to the nursing care of patients who have undergone pituitary tumour surgery using the nasal sphenoid approach. METHODS: This is a prospective research study. In a standard treatment control study, 132 patients undergoing transnasal pituitary tumour surgery were divided into the control group (n = 71) and the observation group (n = 61). The control group was given routine pituitary tumor care, and the "one disease, one product" nursing model was used on the experimental group. The anxiety level of patients, the incidence of postoperative complications, postoperative hospitalization, and levels of satisfaction and capability of group members were measured between the control and experimental groups. RESULTS: There was no difference in the level of anxiety between the 2 groups before admission (P = 0.634). The anxiety level of the patients in the observation group decreased after the "one disease, one product" nursing intervention (P = 0.012), but in the control group, it did not decrease significantly (P = 0.149), and the anxiety level in the control group was significantly higher than in the observation group on day 1 preoperatively (P < 0.001). CONCLUSIONS: "One disease, one product" nursing can reduce the preoperative anxiety and postoperative satisfaction of pituitary adenoma surgery patients through the sphenoid sinus approach. It is worthy of popularization and application in pituitary adenoma resection through the sphenoid sinus approach.

An ultrasound-guided robot assisted system for percutaneous facet joint puncture: an experimental study / 中华创伤骨科杂志

Objective:To evaluate the accuracy of an ultrasound-guided robot-assisted system for percutaneous facet joint puncture in an animal experiment by registration of ultrasound images and two-dimensional X-ray fluorescence images.Methods:Six specimens of fresh adult sheep lumbar spine were prepared and soaked in gelatin solution. The specimens contained a total of 48 facet joints with 24 ones respectively on the left and right sides. Half of the joints were assigned by the random number table method into a robot-assisted group which were subjected to percutaneous facet joint puncture assisted by the ultrasound-guided robot-assisted system while the contralateral ones into a freehand group which were subjected to percutaneous facet joint puncture by freehand. In the robot-assisted group, the left facet joints were 3 L 1, 3 L 2, 3 L 3 and 3 L 4 ones while the right facet joints were 2 L 1, 3 L 2, 5 L 3 and 2 L 4 ones. In this self-control animal experiment, both the robot-assisted punctures and the freehand punctures were carried out in the same specimen. The puncture success rate, puncture needle adjustment, positioning deviation, orientation deviation and operation time were recorded. Results:The positioning deviation and orientation deviation in the robot-assisted group [(2.21 ± 1.12) mm and 1.51° ± 0.47°] were significantly lower than those in the freehand group [(3.26 ± 1.44) mm and 2.24° ± 0.89°] ( P < 0.05). All the articular facet joint punctures were successfully accomplished for the first time in the robot-assisted group while those required multiple adjustments in the freehand group. In the robot-assisted group, the total operation time [(463.84 ± 34.93) s] was significantly longer than that in the freehand group [(298.40 ± 27.48) s], but the puncture time [(37.97 ± 6.87) s] was significantly shorter than that in the freehand group [(261.61 ± 33.15) s] ( P < 0.05). Conclusion:The ultrasound-guided robot-assisted system for percutaneous facet joint puncture can lead to accurate puncture with limited needle adjustments.

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases.

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

microRNA-146a and Hey2 form a mutual negative feedback loop to regulate the inflammatory response in chronic apical periodontitis.

Chronic apical periodontitis (CAP) is defined as chronic inflammation of the dental pulp and root canal system. Porphyromonas endodontalis lipopolysaccharide ( P. endodontalis LPS) plays an important role in inducing an inflammatory response in CAP. microRNA-146a (miR-146a) is a key regulator of inflammation and is induced by LPS. Hairy and enhancer-of-split related with YRPW motif 2 (Hey2) has been confirmed to be induced by the Notch signaling pathway, which is involved in tooth development, pulp regeneration, and repair after injury. Our study aimed to investigate the functional role of miR-146a via the targeting of Hey2 in CAP as well as the underlying mechanism. Compared with 13 healthy controls, miR-146a and Hey2 expressions were significantly higher in 20 patients with CAP. In addition, miR-146a, Hey2, interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α expressions were significantly increased in MC3T3-E1 cells stimulated with different concentrations (0-20 µg/mL) of P. endodontalis LPS for different amounts of time (0-48 hours). Moreover, miR-146a, which acts as an anti-inflammatory mediator, negatively regulated the expression of IL-6, IL-1ß, and TNF-α, and Hey2 was confirmed as a target gene of miR-146a by a luciferase reporter assay. Hey2 also negatively regulated miR-146a, IL-6, IL-1ß, and TNF-α expressions, and P. endodontalis LPS strongly induced Hey2 recruitment to the IL-6 promoter (-400 ~ -200 bp). These findings suggest that miR-146a and Hey2 form a mutual negative feedback regulatory loop, demonstrating a novel mechanism that regulates inflammatory responses in CAP.

Necessity of traditional blackboard in medical genetics teaching in the information age / 基础医学与临床

With the rapid development of multimedia teaching, this article is to declear the necessity of traditional blackboard in the teaching of medical genetics. Multimedia is not a versatile teaching model, and the weakness of the traditional teaching method are increasingly prominent. This article mainly discusses that how blackboard teaching effectively makes up for the deficiencies of multimedia teaching, from the four parts including the integrity of knowledge system, deductive teaching, teaching flexibility and the interaction between teacher and student. Therefore, the traditional blackboard teaching advantages and is very important in the teaching of medical genetics. The reasonable combination of the two teaching methods will sufficiently improve the effectiveness of classroom teaching.

Comparison of effectiveness between micro-plasma technology and 2940 nm Er ∶ YAG laser in treatment of burn scar / 中华医学美学美容杂志

Objective To compare the effectiveness,indications and side effect between microplasma technology (MPT) and 2940 nm Er ∶ YAG laser for treatment of burn scar.Methods 265 patients with hypertrophic scar were treated with MPT (MPT group,N=136) and Er ∶ YAG laser (Er ∶ YAG laser group,N=129).The patients were treated 2-6 times.Results The significant response rate was 73.52 ％ and 44.95 ％ in MPT group and Er ∶ YAG laser group; the cure rate was 28.67 ％ and 15.50 ％ in MPT group and Er ∶ YAG group,respectively.There was no statistically significant difference between two groups (P＞0.05).For moderate burn scar patients (93 cases),the significant response rate was 62.79 ％ and 10.00 ％ in MPT group and Er ∶ YAG laser group,respectively.There was significant difference between two groups (P＜0.05).Conclusions MPT and Er ∶ YAG laser has been proven to be effective and safe for the treatment of burn scar.The effectiveness of MPT is superior to Er ∶ YAG laser in treatment of moderate burn scar.

Malignant tumor-related mortality in crocidolite-contaminated area of Dayao County in Yunnan Province in China: A 27-year retrospective cohort study / 肿瘤

Objective: To investigate the association between environmental exposure (living environment and production environment) to crocidolite and the cancer mortality risk. Methods: A cohort including 1 249 healthy residents recruited from crocidolite-contaminated area in Dayao County, Yunnan Province in 1984 was retrospectively analyzed. The COX regression model was used to estimate hazard ratio (HR ) and 95% confidence interval (CI ) for cancer mortality according to time of exposure to crocidolite and the crocidolite exposure in the production and living environments of blast-furnace manufacturing, material processing, whitewashing the wall, masonry stove building, and starching clothing with slurry. Results: A total of one hundred and twenty-one deaths were identified by April 30, 2011. After adjusting for the confounding factors including age, gender, marriage, education, smoking and alcohol consumption, it was found that as compared with population exposed to crocidolite in five years or less, HRs (95% CIs ) for cancer mortality in populations exposed to crocidolite in 6-10, 11-15 and more than 15 years were 2.898 (1.496-5.616), 4.159 (2.169-7.975), and 4.233 (1.182-9.886), respectively, and a dose-response relationship (P trend<0.05) was observed; compared with population not engaged in production of blast-furnace, the HRs (95% CIs ) for cancer mortality in populations engaged in sporadic production and mass production of blast-furnace were 2.533 (1.549-4.142) and 2.541 (1.642-3.935), respectively; compared with population not engaged in material processing, the HRs (95% CIs ) for cancer mortality in populations using crushing machine in material processing and handcrushing in material processing were 1.811 (1.211-2.709) and 1.785 (1.072-2.793), respectively; the HRs (95% CIs ) for cancer mortality in populations whitewashing the wall for 4 times or more, building the masonry stove and starching clothing with slurry were 1.736 (1.000-3.012), 2.229 (0.97-5.122) and 3.307 (1.522-7.184), respectively. Conclusion: Exposure to crocidolite in living environment and production environment may increase the risk for cancer mortality. Copyright © 2012 by TUMOR.

The changes of palate cleft gap of complete unilateral cleft lip and palate infants before and after presurgical orthodontic and cheiloplasty / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the changes of palate cleft gap of complete unilateral cleft lip and palate (UCLP) infants before and after presurgical orthodontic and cheiloplasty.</p><p><b>METHODS</b>The sample consisted of 18 complete UCLP infants who were treated using presurgical nasoalveolar molding (PNAM) appliance and cheiloplasty. The maxillary models were obtained at the initial visit, after PNAM treatment 1 month before cheiloplasty, and 2 months after cheiloplasty. The change of palate cleft gap were compared.</p><p><b>RESULTS</b>After PNAM treatment and cheiloplasty, the lip profile was obviously improved, cleft gap was reduced, and the height of ala nasi fornix was recovered.</p><p><b>CONCLUSION</b>PNAM treatment can improve the lip shape and nasal deformity degree of UCLP patient. The cleft gap and upper lip tension are reduced.</p>

Assessment of upper jaw extraction versus upper and lower jaw extraction treatment for class II division 1 malocclusion using peer assessment rating index / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To assess the outcome of orthodontic treatment with upper jaw or upper and lower jaw extraction for Class II division 1 malocclusion using the peer assessment rating (PAR) index.</p><p><b>METHODS</b>28 patients with Class II division 1 were extracted two first premolars or second premolars of upper jaw, and 24 patients were extracted four premolars of upper and lower jaw N. The PAR was applied on pre-and post-orthodontic treatment dental casts for the fifty-two cases.</p><p><b>RESULTS</b>The upper and lower jaw extraction groups had significantly higher initial PAR scores and the weighted PAR total scores (P<0.05). Although significantly different before treatment, both groups were not statistically different after treatment (P>0.05).</p><p><b>CONCLUSION</b>The upper and lower jaw extraction cases showed more severe dental displacement. Both treatment can acquire successful results.</p>

The biocharacterization of intrasplenic transplantation of gene modified mouse fetal liver cells / 中华消化杂志

Objective To develop a genetically modified fetal liver cells (FLC) based transplantation system that can release therapeutic levels of hematopoietic growth factors into the system circulation which can facilitate treatment of patient receiving cytokine therapy following chemotherapy. Method Examine adeno virus mediated gene transfer to isolated murine FLC and evaluate the biocharacterization of intrasplenic transplantation of gene modified murine FLC. Results Substantial transfection rate of 80%～85% were achieved at a ratio of 50 for 2 hr of exposure. Gene modified FLC (FLC GM) labeled with 111 In were injected into the allogenic mice, spleen, the %ID/g of liver was 20%～25% at 24 hr and 50%～55% at 48 hr after transplantation. In addition, serum concentration of GM CSF in mice with intrasplenic transplantation reached its maximum at 48 hr [(356 ?58 ) pg/ml]. Conclusion Intrasplenic transplantation of FLC GM can be predominantly localized in liver and spleen, and engraft rapidly and maintain normal function, which represent a critical step toward successfully accomplishing liver directed gene therapy.

Acceleration of the Recovery of Chemotherapy-Induced Immune Suppression by the Intrasplenic Transplantation of GM-CSF Gene-Transfected Fetal Liver Cells / 中国肿瘤生物治疗杂志

After murine fetal liver cells (FLC) were transfected with granulocyte-macrophage colony-stimulating factor (GM-CSF) gene by recombinant adenovirus and intrasplenically transplanted into allogeneic mice, the effects of GM-CSF gene-transfected FLC on the recovery of immune response inhibited by chemotherapy were observed. The number of CD4 + cells and the ratio of CD4 + /CDS + cells from peripheral blood lymphocytes increased significantly. The cytotoxicity of the NK cells and the proliferation response of splenocytes to ConA, LPS elevated markedly, but the same results were not from bone marrow. These data demonstrated that intrasplenic transplantation of GM-CSF gene-transfected FLC could effectively accelerate the recovery of immune response after high-dose chemotherapy.