Abnormal coagulation after hepatectomy in patients with normal preoperative coagulation function.

BACKGROUND: To explore the risk factors for postoperative abnormal coagulation (PAC) and establish a predictive model for patients with normal preoperative coagulation function who underwent hepatectomy. MATERIALS AND METHODS: A total of 661 patients with normal preoperative coagulation function who underwent hepatectomy between January 2015 and December 2021 at the First Affiliated Hospital of Sun Yat-sen University were divided into two groups: the postoperative abnormal coagulation group (PAC group, n = 362) and the normal coagulation group (non-PAC group, n = 299). Univariate and multivariate logistic analyses were used to identify the risk factors for PAC. RESULTS: The incidence of PAC in 661 patients who underwent hepatectomy was 54.8% (362/661). The least absolute shrinkage and selection operator (LASSO) method was used for multivariate logistic regression analysis. The preoperative international normalized ratio (INR), intraoperative succinyl gelatin infusion and major hepatectomy were found to be independent risk factors for PAC. A nomogram for predicting the PAC after hepatectomy was constructed. The model presented a receiver operating characteristic (ROC) curve of 0.742 (95% confidence interval (CI): 0.697-0.786) in the training cohort. The validation set demonstrated a promising ROC of 0.711 (95% CI: 0.639-0.783), and the calibration curve closely approximated the true incidence. Decision curve analysis (DCA) was performed to assess the clinical usefulness of the predictive model. The risk of PAC increased when the preoperative international normalized ratio (INR) was greater than 1.025 and the volume of intraoperative succinyl gelatin infusion was greater than 1500 ml. CONCLUSION: The PAC is closely related to the preoperative INR, intraoperative succinyl gelatin infusion and major hepatectomy. A three-factor prediction model was successfully established for predicting the PAC after hepatectomy.

Engineering of Methionine Adenosyltransferase Reveals Key Roles of Electrostatic Interactions in Enhanced Catalytic Activity.

As an important dietary supplement, S-adenosylmethionine (SAM) is currently synthesized by methionine adenosyltransferase (MAT) using ATP and methionine as substrates. However, the activity of MAT is severely inhibited by product inhibition, which limits the industrial production of SAM. Here, MAT from Bacteroides fragilis (BfMAT), exhibiting relatively low product inhibition and moderate specific activity, was identified by gene mining. Based on molecular docking, residues within 5 Å of ATP in BfMAT were subjected to mutagenesis for enhanced catalytic activity. Triple variants M3-1 (E42M/E55L/K290I), M3-2 (E42R/E55L/K290I), and M3-3 (E42C/E55L/K290I) with specific activities of 1.83, 1.81, and 1.94 U/mg were obtained, which were 110.5-125.6% higher than that of the wild type (WT). Furthermore, compared with WT, the Km values of M3-1 and M3-3 were decreased by 31.4% and 60.6%, leading to significant improvement in catalytic efficiency (kcat/Km) by 322.5% and 681.1%. All triple variants showed shifted optimal pH from 8.0 to 7.5. Moreover, interaction analysis suggests that the enhanced catalytic efficiency may be attributed to the decreased electrostatic interactions between ATP and the mutation sites (E42, E55, and K290). Based on MD simulation, coulomb energy and binding free energy analysis further reveal the importance of electrostatic interactions for catalytic activity of BfMAT, which could be an efficient strategy for improving catalytic performance of MATs.

A nomogram for predicting acute kidney injury following hepatectomy: A propensity score matching analysis.

STUDY OBJECTIVE: The low central venous pressure (LCVP) technique is a key technique in hepatectomy, but its impact on acute kidney injury (AKI) is unclear. The purpose of this study was to explore risk factors (in particular LCVP time) for AKI following hepatectomy. DESIGN: A retrospective case-control study with propensity score matching. SETTING: Operating room. PATIENTS: A total of 1949 patients who underwent hepatectomy were studied. INTERVENTIONS: The patients were grouped with or without AKI within 7 days after surgery. Univariable and multivariable analyses were performed, including recognized intraoperative predictors. The final result is represented as a nomogram. MEASUREMENTS: Preoperative, intraoperative and postoperative data were collected. LCVP is monitored directly through a central venous catheter via the right internal jugular vein. MAIN RESULTS: AKI occurred in 148 patients (7.59%). Surgery time, minimum SBP, furosemide administration and norepinephrine were identified as independent risk factors. The area under the curve for the receiver operating characteristic curves was 0.726 (95% CI 0.668-0.783). CONCLUSION: Intraoperative parameters can be used to predict the probability of postoperative AKI. Although AKI increases the length of stay, it may not increase in-hospital mortality. LCVP time was not confirmed to be a risk factor for AKI.

LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage.

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery.

Discovery of D6808, a Highly Selective and Potent Macrocyclic c-Met Inhibitor for Gastric Cancer Harboring MET Gene Alteration Treatment.

MET alterations have been validated as a driven factor in NSCLC and gastric cancers. The c-Met inhibitors, capmatinib, tepotinib, and savolitinib, are only approved for the treatment of NSCLC harboring exon 14 skipping mutant MET. We used a molecular hybridization in conjunction with macrocyclization strategy for structural optimization to obtain a series of 2-(2-(quinolin-6-yl)ethyl)pyridazin-3(2H)-one derivatives as new c-Met inhibitors. One of the macrocyclic compounds, D6808, potently inhibited c-Met kinase and MET-amplified Hs746T gastric cancer cells with IC50 values of 2.9 and 0.7 nM, respectively. It also strongly suppressed Ba/F3-Tpr-Met cells harboring resistance-relevant mutations (F1200L/M1250T/H1094Y/F1200I/L1195V) with IC50 values of 4.2, 3.2, 1.0, 39.0, and 33.4 nM, respectively. Furthermore, D6808 exhibited extraordinary target specificity in a Kinome profiling against 373 wild-type kinases and served as a promising macrocycle-based compound for further anticancer drug development.

EPAS1 Promoter Hypermethylation is a Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer.

Background: The importance of promoter methylation in non-small cell lung cancers (NSCLC) remains to be understood. Thus, we aimed to determine the diagnostic and prognostic value of the methylation of the endothelial PAS domain containing protein-1 (EPAS1) promoter in NSCLC. Methods: EPAS1 promoter methylation levels were quantitated by methylation-specific PCR. Further, we evaluated the expression, promoter methylation, prognostic value, and impact on immune cell infiltration of EPAS1 by analyzing the TCGA database using web-based bioinformatics tools including GEPIA, UALCAN and MethSurv. Results: Our results demonstrated that promoter methylation of EPAS1 downregulated its expression in NSCLC tissues. Additionally, an AUC value of 0.772 indicated that the methylation of the EPAS1 promoter is a potential diagnostic marker for NSCLC. A Kaplan-Meier analysis demonstrated that high methylation levels of CpG sites in the EPAS1 promoter were indicative of poorer overall survival. Further, EPAS1 expression levels were highly correlated with the infiltration of several types of immune cells, including γδ T cells, T follicular helper cells, CD8+ T cells, and CD4+ T-cells. Conclusion: Collectively, our findings suggest that methylation analyses of the EPAS1 promoter could be used as a prognostic biomarker for NSCLC and that EPAS1 potentially plays an important role in immune cell infiltration in NSCLC.

An immune gene signature to predict prognosis and immunotherapeutic response in lung adenocarcinoma.

Lung adenocarcinoma is one of the most common malignant tumors worldwide. The purpose of this study was to construct a stable immune gene signature for prediction of prognosis (IGSPP) and response to immune checkpoint inhibitors (ICIs) therapy in LUAD patients. Five genes were screened by weighted gene coexpression network analysis, Cox regression and LASSO regression analyses and were used to construct the IGSPP. The survival rate of the IGSPP low-risk group was higher than that of the IGSPP high-risk group. Multivariate Cox regression analysis showed that IGSPP could be used as an independent prognostic factor for the overall survival of LUAD patients. IGSPP genes were enriched in cell cycle pathways. IGSPP gene mutation rates were higher in the high-risk group. CD4 memory-activated T cells, M0 and M1 macrophages had higher infiltration abundance in the high-risk group, which was associated with poor overall survival. In contrast, the abundance of resting CD4 memory T cells, monocytes, resting dendritic cells and resting mast cells associated with a better prognosis was higher in the low-risk group. TIDE scores and the expressions of different immune checkpoints showed that patients in the high-risk IGSPP group benefited more from ICIs treatment. In short, an IGSPP of LUAD was constructed and characterized. It could be used to predict the prognosis and benefits of ICIs treatment in LUAD patients.

Circular RNA atlas in osteoclast differentiation with and without alendronate treatment.

BACKGROUND: Alendronate (AL) is the most widely used bisphosphonate in the treatment of osteoporosis (OP). However, the role of circular RNAs (circRNAs) in the treatment of OP with AL remains unclear. METHODS: In this study, we showed that osteoclast (OC) precursors (OPCSs) could be induced into OCs with macrophage colony-stimulating factor (MCSF) and receptor activator of nuclear factor-κB ligand (RANKL) treatment. Subsequently, the OCs were treated with AL. OC differentiation-related biomarkers including RANK, tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were analyzed with TRAP staining, quantitative real-time (qPCR), and western blotting. Differentially expressed circRNAs (DECs) were identified among the OPCS, OC, and OC + AL groups. In addition, the expression levels of 10 DECs related to OC differentiation were verified by qPCR. RESULTS: TRAP staining showed that MCSF and RANKL treatment effectively induced OPCSs to differentiate into OCs. In addition, qPCR and western blot analysis revealed that the three biomarkers of OC (RANK, TRAP, and CTSK) were expressed significantly more in the OC group than those in the OPCS group. In contrast, the mRNA and protein expression levels of these three biomarkers decreased significantly in OCs treated with AL compared with those non-treated OCs. GO analysis of the DECs in the OPCS group vs. the OC group revealed that their functions were mainly related to cell, cell part, binding, and single-organism terms. KEGG analysis of the top 20 DECs in a comparison between the OPCS and OC groups showed that genes involved in mitogen-activated protein kinase signaling were the most common. Results of functional analyses of DECs in an OC vs. OC + AL comparison were similar to those in the OPCS vs. OC comparison. Finally, qPCR showed that, in the OC + AL vs. OC group comparison, the expression levels of seven and three DECs significantly decreased and increased, respectively. CONCLUSIONS: Having successfully induced OPCSs to differentiate into OCs, we showed that AL suppresses the differentiation of OPCS into OC and that 10 DECs were involved in the regulation of this process. This indicates that these DECs might be important to the treatment of OP.

Tanshinone IIA reverses EGF- and TGF-ß1-mediated epithelial-mesenchymal transition in HepG2 cells via the PI3K/Akt/ERK signaling pathway.

Epithelial-to-mesenchymal transition (EMT) is an essential phenotypic conversion involved in cancer progression. Epidermal growth factor (EGF) and transforming growth factor (TGF)-ß1 are potent inducers of the EMT. Tanshinone IIA (Tan IIA) is a phenanthrenequinone extracted from the root of Salvia miltiorrhiza Bunge, and its anticancer activity has been demonstrated in numerous studies. However, the mechanisms of action underlying Tan IIA in EGF- and TGF-ß1-induced EMT in HepG2 cells remain unknown. Multiple assays were utilized in the present study, including colony formation, wound healing, Transwell invasion, immunofluorescence staining and western blotting, in order to assess the influence of Tan IIA on HepG2 cells induced by 20 ng/ml EGF and 10 ng/ml TGF-ß1. The present study reported that Tan IIA treatment decreased EGF- and TGF-ß1-enhanced cell colony numbers, migration and invasion, and inhibited EGF- and TGF-ß1-induced decreases in the expression levels of E-cadherin, and increases in the expression levels of matrix metalloproteinase-2, N-cadherin, vimentin and Snail. In addition, it was observed that Tan IIA decreased the expression levels of phosphorylated (p)-Akt and p-ERK1/2 induced by EGF and TGF-ß1. Furthermore, western blot analysis confirmed that blocking the function of PI3K/Akt and ERK with LY294002 and U0126 resulted in upregulation of E-cadherin expression, and downregulation of vimentin and Snail expression in EGF- and TGF-ß1-treated HepG2 cells. In conclusion, to the best of our knowledge, the results of the present study are the first to indicate that Tan IIA may suppress EGF- and TGF-ß1-induced EMT in HepG2 cells by deactivating the PI3K/Akt/ERK pathway.

Co-culture of the bone and bone marrow: a novel way to obtain mesenchymal stem cells with enhanced osteogenic ability for fracture healing in SD rats.

BACKGROUND: Mesenchymal stem cells (MSCs) have great potential for the repair and regeneration of bone fracture, but their optimal origins remain controversial. METHODS: Bone marrow-MSCs (BM-MSCs) and bone-bone marrow-MSCs (B-BM-MSCs) were isolated from 12 SD rats, and the morphology, MSC-associated markers, and proliferative capacity of these cells were compared using an inverted microscope, flow cytometry, and CCK-8 assays, respectively. After 14 days of osteoblastic induction, osteoblast phenotypes were detected by ALP and calcium nodule staining, and the expression of BMP-2 and TGF-ß1 was observed by western blotting. Then, the rat tibia fracture model was established with 3 groups (n = 6 per group), the control, BM-MSC, and B-BM-MSC groups. Computed tomography (CT) imaging was performed to evaluate fracture healing at weeks 2, 4, and 6. Finally, the fractured bones were removed at weeks 4 and 6, and HE staining was performed to evaluate fracture healing. RESULTS: Although the 2 types of MSCs shared the same cellular morphology and MSC-associated markers, B-BM-MSCs had a higher proliferative rate than BM-MSCs from day 9 to day 12 (p < 0.05), and the expression levels of ALP and calcium were obviously higher in B-BM-MSCs than in BM-MSCs after osteogenic induction (p < 0.01 and p < 0.001, respectively). Western blot results showed that the expression levels of BMP-2 and TGF-ß1 in B-BM-MSCs were higher than in BM-MSCs before and after osteogenic induction (p < 0.01). In the animal experiments, CT imaging and gross observation showed that B-BM-MSCs had a greater capacity than BM-MSCs to promote fracture healing, as the Lane-Sandhu scores of B-BM-MSCs at weeks 4 and 6 after operation (3.00 ± 0.81 and 9.67 ± 0.94, respectively) were higher than those of BM-MSCs (1.33 ± 0.47 and 6.67 ± 1.25, respectively; both p < 0.05). The HE staining results further supported this conclusion. CONCLUSIONS: Taken together, our study results proved that MSCs obtained by co-culturing the bone and bone marrow from SD rats had better proliferative, osteogenic differentiation, and fracture healing capacities than BM-MSCs, perhaps suggesting a novel way to obtain MSCs for bone tissue repair.

Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3.

BACKGROUND: Microglial polarization with M1/M2 phenotype shifts and the subsequent neuroinflammatory responses are vital contributing factors for spinal cord injury (SCI)-induced secondary injury. Nuclear factor-κB (NF-κB) is considered the central transcription factor of inflammatory mediators, which plays a crucial role in microglial activation. Lysine acetylation of STAT1 seems necessary for NF-kB pathway activity, as it is regulated by histone deacetylases (HDACs). There have been no studies that have explained if HDAC inhibition by valproic acid (VPA) affects the NF-κB pathway via acetylation of STAT1 dependent of HDAC activity in the microglia-mediated central inflammation following SCI. We investigated the potential molecular mechanisms that focus on the phenotypic transition of microglia and the STAT1-mediated NF-κB acetylation after a VPA treatment. METHODS: The Basso-Beattie-Bresnahan locomotion scale, the inclined plane test, the blood-spinal cord barrier, and Nissl staining were employed to determine the neuroprotective effects of VPA treatment after SCI. Assessment of microglia polarization and pro-inflammatory markers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and interferon (INF)-γ was used to evaluate the neuroinflammatory responses and the anti-inflammatory effects of VPA treatment. Immunofluorescent staining and Western blot analysis were used to detect HDAC3 nuclear translocation, activity, and NF-κB signaling pathway activation to evaluate the effects of VPA treatment. The impact of STAT1 acetylation on NF-kB pathway and the interaction between STAT1 and NF-kB were assessed to evaluate anti-inflammation effects of VPA treatment and also whether these effects were dependent on a STAT1/NF-κB pathway to gain further insight into the mechanisms underlying the development of the neuroinflammatory response after SCI. RESULTS: The results showed that the VPA treatment promoted the phenotypic shift of microglia from M1 to M2 phenotype and inhibited microglial activation, thus reducing the SCI-induced inflammatory factors. The VPA treatment upregulation of the acetylation of STAT1/NF-κB pathway was likely caused by the HDAC3 translocation to the nucleus and activity. These results indicated that the treatment with the VPA suppressed the expression and the activity of HDAC3 and enhanced STAT1, as well as NF-κB p65 acetylation following a SCI. The acetylation status of NF-kB p65 and the complex with NF-κB p65 and STAT1 inhibited the NF-kB p65 transcriptional activity and attenuated the microglia-mediated central inflammatory response following SCI. CONCLUSIONS: These results suggested that the VPA treatment attenuated the inflammatory response by modulating microglia polarization through STAT1-mediated acetylation of the NF-κB pathway, dependent of HDAC3 activity. These effects led to neuroprotective effects following SCI.

Effects of single-port laparoscopic percutaneous extraperitoneal closure on the orientation of the vas deferens and testicular perfusion and volume: Experience from a single center.

OBJECTIVE: To investigate the influence of single-port laparoscopic percutaneous extraperitoneal closure (LPEC) on the orientation of the vas deferens and testicular perfusion and volume in pediatric patients undergoing inguinal hernia repair. METHODS: A total of 92 consecutively enrolled boys preoperatively diagnosed with a unilateral inguinal hernia underwent single-port LPEC between June 2013 and June 2014. The orientation of the vas deferens and the testicular perfusion and volume of these patients were ultrasonographically assessed preoperatively, one month after surgery and six months after surgery. RESULTS: The surgical procedures were performed successfully without conversion or serious perioperative complications. Ultrasonography showed no angulation or distortion of the vas deferens on the surgical side during a six-month follow-up period. Similarly, there were no perioperative changes in testicular perfusion or volume. CONCLUSION: Our experience suggests that the single-port LPEC technique can be safe and effective in pediatric patients with an inguinal hernia and that this technique does not affect the orientation of the vas deferens or testicular perfusion or volume.

Application of a Laparoscopic, Single-port, Double-needle Technique for Pediatric Hydroceles With Multiple Peritoneal Folds: A Trial From a Single-center 5-Year Experience.

OBJECTIVE: To report our 5-year experience with a modified single-port, double-needle, minilaparoscopic technique for patent processus vaginalis with multiple peritoneal folds in the hydrocele sac orifice. METHODS: A total of 125 consecutive cases of boys with unilateral pediatric hydrocele underwent minilaparoscopic repair between June 2008 and June 2013. The patients were divided into 2 groups. Group 1 consisted of 65 patients who underwent a 2-port laparoscopic procedure, during which a 3-mm grasping forceps was used to grasp the folds around the internal inguinal ring. Group 2 included 60 patients who received a modified single-port, double-needle, minilaparoscopic surgery. An Endo Close needle was used to spread the peritoneal folds and facilitate circular extraperitoneal suturing in group 2. The principal outcome factors were assessed between the groups. RESULTS: A total of 151 minilaparoscopic procedures were performed in 125 patients (age range, 12-68 months; median, 21.5 months). In total, 26 extra procedures were performed for simultaneous repair of a potential contralateral patent processus vaginalis. No significant difference in operation time was noted between group 1 and group 2 (25.9 ± 6.4 vs 27.1 ± 5.5 minutes). The procedures were performed successfully without serious preoperative complications. During a median follow-up period of 18 months (range, 6-36 months), no postoperative hydrocele recurrence was encountered. CONCLUSION: Our limited experience suggests that the modified single-port, double-needle, minilaparoscopic technique could be safe, effective, and more cosmetically appealing for the management of complicated pediatric hydroceles.

[The standardized practice of laparoscopic-assisted radical right hemicolectomy in order to achieve complete mesocolic excision].

OBJECTIVE: To explore the feasibility of laparoscopic-assisted radical right hemicolectomy with the outcome being a complete mesocolic excision (CME). METHODS: Between February 2010 and June 2011, we performed the standardized surgery of laparoscopic-assisted radical right hemicolectomy with an aim of CME on 14 patients. There were 10 males and 4 females, with an average age of 57 years (range 36 to 74 years). All the pathologic results in 14 cases were primary colonic adenocarcinoma. The TNM stages were distributed as follows: 2 in II A, 3 in II B, 3 in III A, 5 in III B and 1 in III C. RESULTS: Surgery was successfully performed for all patients without open conversion. The average operation time was (178 ± 37) minutes (range 127 to 221 minutes), average intraoperative blood loss was (67 ± 23) ml (range 30 to 110 ml), while the average number of lymph node harvest was 21 ± 7 (range 14 to 31), and the postoperative hospital stay was (10.0 ± 2.2) days (range 7 to 15 days). Minor complications occured in 2 patients. Major complications and post-operative mortality were not observed. All the patients were followed up for 3 to 19 months, no tumor recurrence or metastasis was identified. CONCLUSION: The standardized surgery of laparoscopic-assisted radical right hemicolectomy with the final outcome of CME is safe and feasible.

Expression of heat shock protein 27 in the esophageal tissue of rats with reflux esophagitis.

BACKGROUND: Little attention has been paid to the expression of heat shock protein 27 (HSP27) in patients with reflux esophagitis (RE), and few studies of the importance of HSP27 in esophagitis have been carried out in animal models. This study aimed to explore the expression of HSP27 in the esophageal tissue of rats with RE. METHODS: Eighty female Wistar rats were randomly divided into experimental groups A and B and control groups C and D (n = 20 in each group). To establish RE, rats in the two experimental groups received pylorus and forestomach ligations, while rats in the control group received gastrostomy and gastric perforation repair. The rats in groups A and C were sacrificed 7 days after surgery, and the rats in groups B and D were sacrificed 14 days after surgery. In groups A and B, 10 and 8 rats were diagnosed with RE by pathological examination, respectively (they were included in groups A' and B', respectively). The histopathological diagnosis of all the lower esophageal tissues in groups C and D was normal and 20 normal specimens were randomly selected for groups C' and D' with 10 specimens in each group. Macroscopic and microscopic esophagitis scores were assessed for the specimens in groups A' and B'. Lower esophageal tissues were collected from groups A', B', C', and D', and paraffin-embedded slices were made using part of the tissues. The expression of HSP27 in the tissues was detected using the two-step streptavidin-peroxidase immunohistochemical method. Some collected tissues were frozen, and expressions of HSP27 mRNA were detected using fluorescence quantitative polymerase chain reaction (FQ-PCR). RESULTS: Median macroscopic and microscopic esophagitis scores in groups A' (n = 10) and B' (n = 8) were 1.0 and 1.5, and 2.0 and 2.5, respectively. There were no significant differences in the macroscopic or microscopic esophagitis scores between the two groups (Z = -0.330, P = 0.741; Z = -0.142, P = 0.887, respectively). Immunohistochemical staining showed that HSP27 was expressed in all layers of the esophageal epithelia in RE and control rats. FQ-PCR showed that HSP27 mRNA levels in the lower esophageal tissue in RE group (groups A' and B') were higher than those in control group (groups C' and D') (Z = -0.249, P = 0.001). HSP27 mRNA expression in the lower esophageal tissue was significantly different in groups B' and D' (Z = -3.027, P = 0.002). And the levels of HSP27 mRNA expression in severe RE group (microscopic esophagitis score: 3) were higher than in mild RE group (microscopic esophagitis score: 1-2) and control group (Z = -3.396, P = 0.001; Z = -3.855, P < 0.001). CONCLUSIONS: HSP27 mRNA expression in the lower esophageal tissue of rats with RE is significantly higher than in the normal controls. Although reflux is a persistent stimulating factor, increased expression of HSP27 in the lower esophageal tissue of rats with RE requires aggravated esophageal injury.

Effect of botulinum toxin type A on transforming growth factor beta1 in fibroblasts derived from hypertrophic scar: a preliminary report.

BACKGROUND: Hypertrophic scar is a common dermal disease. Numerous treatments are currently available but they do not always yield excellent therapeutic results. Hence, alternatives are needed. Recent basic and clinical research has shown that botulinum toxin type A (BTXA) has antihypertrophic scar properties but the molecular mechanism for this action is unknown. The aim of this study was to explore the effect of BTXA on transforming growth factor beta1 (TGF-beta1) in fibroblasts derived from hypertrophic scar and further elucidate its actual mechanism. METHODS: Fibroblasts were isolated from tissue specimens of hypertrophic scar. Fibroblasts were treated with BTXA and the difference in proliferation between treated and nontreated cells was analyzed through the MTT method from the first to the fifth day after treatment. Proteins of TGF-beta1 were checked using ELISA in fibroblasts with BTXA and without BTXA from the first to the fifth day. RESULTS: The growth of the fibroblast treated with BTXA was obviously slower than that of the fibroblast without BTXA treatment (p < 0.01), which showed that BTXA effectively inhibited the growth of fibroblasts. Proteins of TGF-beta1 between fibroblasts with BTXA and fibroblasts without BTXA are statistically significant (p < 0.01). CONCLUSION: These results suggest that BTXA effectively inhibited the growth of fibroblasts derived from hypertrophic scar and in turn caused a decrease in TGF-beta1 protein, indicating that BTXA-based therapies for hypertrophic scar are promising and worth investigating further.

[Analysis of differences on delineation of the gross tumor volume (GTV) of nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Accurate delineation of tumor target volume and organ at risk based on CT simulation, is essential in modern radiotherapy planning. It is also the basic requirement to improve the treatment outcome and quality of life in nasopharyngeal carcinoma (NPC). In this study, the impact factors on delineation of the gross tumor volume (GTV) of NPC were analysis. by comparing difference among various doctors' contours. METHODS: Thirty cases of NPC treatment planning with contrast enhanced CT scan were reviewed. Primary GTV delineated by in-charged physician was defined as GTV1. Another GTV delineated by author and a radiologist was defined as GTV2, while GTV1 was concealed by the functions of the treatment planning system, the longest diameters of each axis of GTV were measured and recorded respectively as X(1), Y(1), Z(1), and X(2), Y(2), Z(2). The volumes of GTV were calculated as V1 and V2. Maximum permitted error (MPE) was 2 mm on X and Y axes and 3 mm on Z axis. Margin of each axis was compared to Coparable MPEs by matching t-test. RESULTS: The differences on axes of X, Y, Z between GTV1 and GTV2 were 2.95+/-4.33, 6.24+/-7.52, 6.25+/-9.35, respectively (P