High preoperative plasma fibrinogen and serum albumin score is associated with poor survival in operable esophageal squamous cell carcinoma.

This study was performed to investigate the prognostic significance of a cumulative score based on the preoperative plasma fibrinogen and serum albumin (FA score) in operable esophageal squamous cell carcinoma (ESCC). Clinicopathologic characteristics, preoperative fibrinogen, and albumin concentrations were retrospectively reviewed in patients who underwent transthoracic esophagectomy. The optimal cutoff value was defined as 4.0 g/L for fibrinogen according to previous studies and as 41.0 g/L for albumin for the lower quartile. Subjects with elevated fibrinogen and decreased albumin levels were allocated a score of 2, those with only one of these two abnormalities were assigned a score of 1, and those with neither of the abnormalities were allocated a score of 0. The preoperative FA score was significantly associated with tumor length, depth of invasion, lymph node involvement, tumor-node-metastasis (TNM) stage, and the modified Glasgow Prognostic Score (mGPS). No significant differences in age, gender, tumor location, degree of differentiation, smoking or alcohol consumption were found between groups. Univariate survival analysis revealed that high preoperative FA score (1/2) was significantly associated with unfavorable disease-free survival (DFS) [hazard ratio (HR), 1.675; 95% confidence interval (CI), 1.278-2.195; P < 0.001] and overall survival (OS) (HR, 1.685; 95% CI, 1.268-2.239; P < 0.001). Furthermore, it remained an independent prognostic indicator for both DFS (HR, 1.394; 95% CI, 1.035-1.879; P = 0.029) and OS (HR, 1.369; 95% CI, 1.010-1.878; P = 0.048) in multivariable Cox regression analysis. A high preoperative FA score could significantly predict impaired long-term survival for ESCC patients who underwent transthoracic esophagectomy.

Myosin VI contributes to maintaining epithelial barrier function.

BACKGROUND: Epithelial barrier dysfunction is associated with the pathogenesis of a number of immune inflammations; the etiology is not fully understood. The fusion of endosome/lysosome is a critical process in the degradation of endocytic antigens in epithelial cells. Recent reports indicate that myosin VI (myo6) is involved in the activities of endosomes. The present study aims to investigate the role of myo6 in epithelial barrier dysfunction. RESULTS: The endosome accumulation was observed in myo6-deficient Rmcs. More than 80% endosomes were fused with lysosomes in naïve Rmcs while less than 30% endosomes were fused with lysosomes in the myo6-deficient Rmcs. The myo6-deficient Rmc monolayers showed high permeability to a macromolecular antigen, ovalbumin, the latter still conserved the antigenicity, which induced strong T cell activation. CONCLUSIONS: We conclude that myo6 plays a critical role in the fusion of endosome/lysosome in Rmc epithelial cells. Deficiency of myo6 compromises the epithelial barrier function.

Sustained-release oxycodone tablets for moderate to severe painful diabetic peripheral neuropathy: a multicenter, open-labeled, postmarketing clinical observation.

OBJECTIVE: To evaluate the efficacy and safety of sustained-release (SR) oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy (DPN). Design. This was a multicenter, randomized, open-labeled study. SETTING: This study was completed in 12 hospitals in China. PATIENTS: A total of 80 Chinese patients undergoing moderate to severe painful DPN. INTERVENTIONS: An initial dose of 10mg is recommended to be taken orally every 12 hours. Dose titration was done appropriately according to pain intensity and adverse reactions. OUTCOME MEASURES: Data record included days, dosage, analgesic efficacy, quality of sleep, adverse events, and combination therapy when patients were treated with SR oxycodone tablets. The continuous observation period was 6 weeks. RESULTS: After medication for 1 week, pain was significantly (P<0.01) relieved from 6.8±1.4 to 2.8±1.6. Onset time was within 45 minutes in nearly 60% of the patients, and within 1 hour in nearly 95% of that ones. More than 90% of the patients achieved stable analgesic dose within 3 days. After using SR oxycodone tablets for 1 week, sleep quality was significantly (P<0.01) improved. In week 1, the average dose of SR oxycodone tablets was 16.63±7.79mg. The average daily dose of most patients was about 20mg after 2 weeks. In all the enrolled patients, 38 (47.5%) had adverse reactions. No serious adverse reactions took place. CONCLUSION: The results of this clinical observation further elaborated the efficacy and safety of SR oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy in China.

Review of the genus Larnaca Walker, 1869 from China (Orthoptera: Gryllacrididae: Gryllacridinae).

The Chinese species of Larnaca are reviewed. A new species, Larnaca (Larnaca) walle sp. nov. is described from China. Female of Larnaca (Larnaca) emarginata Bian, Guo Shi, 2015 is described for the first time. The type specimen is deposited in Museum of Biology, East China Normal University.

Exosomal lncRNA LINC01711 facilitates metastasis of esophageal squamous cell carcinoma via the miR-326/FSCN1 axis.

Esophageal cancer is a malignant tumor with a five-year survival rate of less than 20%. Early diagnosis and exploration of esophageal cancer pathogenesis are of great significance for the treatment and prognosis of esophageal cancer. Long non-coding RNA (lncRNA) plays a vital role in the occurrence and development of different types of tumors. However, the role of exosome LncRNA in esophageal squamous cell carcinoma (ESCC) is rarely reported. In this study, we detected high expression of lncRNA LINC01711 in ESCC tissues and was associated with poor prognosis. Silencing LINC01711 can inhibit the proliferation, migration, invasion, and growth of ESCC cell lines, and induce apoptosis. Linc01711 was identified as a competitive endogenous RNA that suppressed miR-326, and up-regulated the expression of fascin actin-bundling protein 1 (FSCN1). Besides, in vivo experiments showed that the administration of exosome-derived LINC01711 (LINC01711-Exo) promoted the growth of tumors in nude mice. In general, exosomal LINC01711 promoted the proliferation, migration, and invasion of esophageal cancer cells by up-regulating FSCN1 and down-regulating miR-326, thus improved the occurrence and development of ESCC.

Exploring the sulfate patterns of chondroitin sulfate/dermatan sulfate and keratan sulfate in human pancreatic cancer.

This study was designed to explore the sulfation patterns of chondroitin sulfate (CS)/dermatan sulfate (DS), and keratan sulfate (KS) and the expression of carbohydrate sulfotransferases (CHSTs) in 26 pancreatic tumor and normal tissues. CS/DS and KS profiles were simultaneously determined. Pancreatic tumor tissues exhibited increased ΔDi-0S, ΔDi-4S, and ΔDi-6S levels, with absolute ΔDi-4S content being highest, followed by ΔDi-6S. However, as for the contents of KS-6S and KS-6S,6'S, there were no significant regular change. The expression levels of CHST1 and CHST4 were 37 and 15 times higher than those in normal tissues. PCA and OPLS-DA revealed that ΔDi-4S and ΔDi-6S levels could be reliably used to differentiate between healthy and cancerous tissues. The up-regulation of CHST3, CHST12, CHST13, and CHST15 was directly correlated with C-4 and C-6 sulfation. These data provide a foundation for future studies of the role of ΔDi-4S and ΔDi-6S in the progression of pancreatic cancer.

[The "wake-up correction" for preventing spinal cord injury in scoliosis surgery].

OBJECTIVE: To observe the effects of "wake-up correction" technique for preventing iatrogenic spinal cord injury in scoliosis surgery. METHODS: Twenty-one patients who had scoliosis with Cobb's angle 92 degrees - 145 degrees received operation of pedicle screw insertion in all or important vertebral bodies, release of stiff segments, decompression and osteotomy. All the patients were trained how to wake up before anesthesia. Maintenance of anesthesia was achieved with infusion of propofol at target-controlled concentration 3-4 mg/L and remifentanil at 0.15 microg/(kg.min). Fresh gas 2 L/min of N(2)O:O(2) 1:1 was inhaled during mechanical ventilation. Wake-up methods:the muscle relaxant was stopped injection 30 min before wake-up, decreasing propofol's target-controlled concentration to 1-2 mg/L and remifentanil to 0.05 - 0.10 microg/(kg x min). Once the spontaneous respiration returned, woke up the patients and asked them move both toes following our orders (the first wake-up). Then patients inhaled 6% sevoflurane in fresh gas 6 L/min (N(2)O:O(2) 1:1). When the end-tidal anesthetic gas concentration was arrived 1.3 - 1.5 MAC, all of the anesthetics were stopped. The correction operation was completed and the patient was woke up again (the second wake-up). Recorded data included time used to wake up, directive action returning time, whether the patient had memory of wake-up during operation when following up. RESULTS: All patients woke up with satisfaction. The time taken the first wake-up was (10.3 + or - 4.5) min, and for the second was (4.3 + or - 2.3) min. There were two patients who had slightly agitation during correction. There was no one who had neurological injury. There was no memory of wake-up and no pain in all patients during operation. Cobb' angle was corrected to 22 degrees - 38 degrees (average 29 degrees ), and the correction rate was 74%. CONCLUSION: The "wake-up correction" is effective and satisfactory by detecting the cord function in time.

[The expression and significance of nerve growth factor and its receptors in pancreatic ductal adenocarcinoma].

OBJECTIVE: To investigate nerve growth factor (beta-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. METHODS: Expression and distribution of beta-NGF, tyrosine kinase A (TrKA) and P75(NGFR) were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of beta-NGF and its receptors with clinical pathological characters, especially nerve invasion were analyzed. RESULTS: beta-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0.01). beta-NGF and TrKA expression are associated with the differentiation grades (DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of beta-NGF and TrKA. beta-NGF and TrKA expression have positive correlations. beta-NGF, TrKA and P75(NGFR) mRNA expression have significantly increased 3.84, 4.23 and 2.41 times than normal tissues by real-time PCR, respectively. CONCLUSIONS: beta-NGF and TrKA might play potential roles in carcinogenesis for pancreatic cancer, have affinity with clinicopathological characters of pancreatic cancer. beta-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.

Silencing of perilipin by short hairpin RNA inhibits proliferation and induces apoptosis in liposarcoma cells.

Previous studies have identified that perilipin-1 (PLIN1) is a highly specific marker for liposarcoma. However, its functions have yet to be fully elucidated. The aim of the present study was to investigate the potential role of PLIN1 in the proliferation, migration and apoptosis of liposarcoma cells. Short hairpin RNA was designed to inhibit PLIN1 levels. Cell proliferation was monitored by Cell Counting Kit­8 assay and cell migration determined by wound healing assay. Flow cytometry was performed to assess the cell cycle distributions and apoptosis in liposarcoma cells. The results demonstrated that the expression of PLIN1 was significantly upregulated in liposarcoma tumor tissues compared with normal adipose tissues. Silencing of PLIN1 by short hairpin RNA significantly inhibited proliferation and migration and induced G1 phase cell cycle arrest and apoptosis in liposarcoma cell lines. It was identified that PLIN1 serves a crucial role in the pathogenesis and progression of liposarcoma and may be a potential therapeutic target for its clinical management.

Trastuzumab modified silica nanoparticles loaded with doxorubicin for targeted and synergic therapy of breast cancer.

Untargeted delivery as well as low efficacy are two main obstacles for effective breast cancer therapy. Here in this study, we surface modified silica nanoparticles (SLN) with Trastuzumab (Tra) to construct a tumor-targeting carrier (Tra-SLN) for specific drug delivery to human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells. In addition, Tra-SLN could also loaded with broad-spectrum anticancer drug doxorubicin (DOX) to finally construct a drug delivery system (DDS) capable of co-delivering Tra and DOX (Tra-SLN/DOX). Our results demonstrated that the as-prepared Tra-SLN/DOX was nanoscale particles with spheroid appearance which showed preferable stability in physiological environments. In addition, the Tra-SLN/DOX could specifically target to HER2 overexpressed MCF-7 cells. Both in vitro and in vivo experiments revealed that the Tra-SLN/DOX exerted enhanced anticancer efficacy when compared with Tra or DOX alone. It was suggested that Tra-SLN/DOX might be a promising platform for enhanced therapy of breast cancer.

Hyperbaric oxygen treatment at various stages following chronic constriction injury produces different antinociceptive effects via regulation of P2X4R expression and apoptosis.

PURPOSE: The aims of this study were to investigate the effect of hyperbaric oxygen (HBO) treatment at various stages following chronic constriction injury (CCI) and to explore the underlying mechanisms of HBO treatment. METHODS: Forty adult male Sprague-Dawley rats were randomly assigned to five groups (n = 8 for each group): the sham group, CCI group, HBO1 group, HBO2 group, and HBO3 group. Neuropathic pain was induced by CCI of the sciatic nerve. HBO treatment began on postoperative days 1, 6, and 11 and continued for 5 days. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. The expression of P2X4R was determined by immunohistochemistry and western blot analysis. Cell apoptosis was measured using TUNEL staining. The expression of caspase 3 was measured using reverse transcription polymerase chain reaction (RT-PCR). Electron microscopy was used to determine the ultrastructural changes. RESULTS: Early HBO treatment beginning on postoperative day 1 produced a persistent antinociceptive effect and inhibited the CCI-induced increase in the expression of P2X4R without changing CCI-induced apoptosis. In contrast, late HBO treatment beginning on postoperative day 11 produced a persistent antinociceptive effect and inhibited CCI-induced apoptosis and upregulation of caspase-3 without changing the expression of P2X4R. In addition, late HBO treatment reduced CCI-induced ultrastructural damage. However, HBO treatment beginning on postoperative day 6 produced a transient antinociceptive effect without changing the expression of P2X4R or CCI-induced apoptosis. CONCLUSION: HBO treatment at various stages following CCI can produce antinociceptive effects via different mechanisms. Early HBO treatment is associated with inhibition of P2X4R expression, and late HBO treatment is associated with inhibition of cell apoptosis.

Hyperbaric oxygen treatment produces an antinociceptive response phase and inhibits astrocyte activation and inflammatory response in a rat model of neuropathic pain.

Hyperbaric oxygen (HBO) treatment has been proven to be a promising candidate for protection of the nervous system after acute injury in animal models of neuropathic pain. The purposes of this study were to examine the antinociceptive response phase induced by HBO treatment in a model of neuropathic pain and to determine the dependence of the treatment's mechanism of alleviating neuropathic pain on the inhibition of spinal astrocyte activation. Neuropathic pain was induced in rats by chronic constriction injury of the sciatic nerve. Mechanical threshold and thermal latency were tested preoperatively and for 1 week postoperatively, four times daily at fixed time points. Methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) parameters were used as indices of oxidative stress response and tested before and after the treatment. The inflammatory cytokines interleukin (IL)-1ß and IL-10 were assayed in the sciatic nerve were with enzyme-linked immunoassay. Glial fibrillary acidic protein activation in the spinal cord was evaluated immunohistochemically. The rats exhibited temporary allodynia immediately after HBO treatment completion. This transient allodynia was closely associated with changes in MDA and SOD levels. A single HBO treatment caused a short-acting antinociceptive response phase. Repetitive HBO treatment led to a long-acting antinociceptive response phase and inhibited astrocyte activation. These results indicated that HBO treatment played a dual role in the aggravation and alleviation of neuropathic pain, though the aggravated pain effect (transient allodynia) was far less pronounced than the antinociceptive phase. Astrocyte inhibition and anti-inflammation may contribute to the antinociceptive effect of HBO treatment after nerve injury.

Effects of hyperbaric oxygen on pain-related behaviors and nitric oxide synthase in a rat model of neuropathic pain.

BACKGROUND: Neuropathic pain is complex, and a satisfactory therapeutic method of treatment has yet to be developed; therefore, finding a new and effective therapeutic method is an important issue in the field of neuropathic pain. OBJECTIVE: To determine the effects of hyperbaric oxygen (HBO) on pain-related behaviours and nitric oxide synthase (NOS) expression in a rat model of neuropathic pain. METHODS: Forty male Sprague Dawley rats were randomly divided into five groups (eight rats per group) including control, sham operation, sciatic nerve with chronic constriction injury (CCI), HBO pretreatment (pre-HBO) and HBO post-treatment (post-HBO) groups. Pain-related behaviours and NOS expression in the spinal cord were compared among the five groups. RESULTS: Compared with the CCI group, the mechanical withdrawal threshold was significantly increased and thermal withdrawal latency was significantly extended in the pre-HBO and post-HBO groups (all P<0.05). After CCI, expression of spinal neuronal NOS and inducible NOS were increased. Expression of spinal neuronal NOS and inducible NOS were significantly decreased in the pre-HBO and post-HBO groups compared with the CCI group (all P<0.05). Spinal eNOS expression changed very little. DISCUSSION: HBO has been used as an effective and noninvasive method for the treatment of spinal cord injuries and high-altitude sickness, and in immunosuppression and stem-cell research; however, it has yet to be applied to the treatment of neuropathic pain. The present study indicated that HBO effectively increased mechanical withdrawal threshold and thermal withdrawal latency, demonstrating that HBO has therapeutic effects on neuropathic pain. CONCLUSION: HBO inhibits pain in rats with CCI through the regulation of spinal NOS expression.

Prevention of propofol-induced pain in children: pretreatment with small doses of ketamine.

STUDY OBJECTIVE: To evaluate the efficacy of ketamine in preventing propofol injection pain in children. DESIGN: Prospective, randomized, double-blinded, placebo-controlled study. SETTING: University-affiliated hospital. PATIENTS: 192 ASA physical status 1 and 2 pediatric patients. INTERVENTIONS: Patients were randomly assigned to 4 groups. Group S (control) received normal saline as a placebo; Group K1, Group K3, and Group K5 received 0.1 mg/kg, 0.3 mg/kg, and 0.5 mg/kg of ketamine, respectively. Fifteen seconds after the ketamine injection, patients were injected with propofol at a rate of 12 mL/min until loss-of-eyelash reflex. MEASUREMENT: Pain was evaluated blindly at the time of induction using a 4-point scale: 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain. Adverse effects were recorded. Characteristics of induction of anesthesia, such as dose of propofol and time from propofol injection to loss of consciousness (induction duration), were noted. MAIN RESULTS: 39 (84.8%) Group S (control) patients had pain. Pretreatment with ketamine reduced the frequency of pain significantly to 56.5%, 17.0%, and 14.9% in Groups K1, K3, and K5, respectively. Furthermore, the frequency of moderate and severe pain in Group K1 (21.8%), Group K3 (6.4%), and Group K5 (4.3%) was significantly (P < 0.001, respectively) reduced compared with Group S (76.1%). Moreover, the dose of propofol for induction in Group K5 was smaller than in Group S, Group K1, and Group K3 (P < 0.05). One patient in Group K5 had emergence agitation. CONCLUSION: Pretreatment with a small dose of ketamine (0.3 mg/kg) reduced the frequency and intensity of propofol injection pain without severe adverse effects.

Neurotrophic artemin promotes motility and invasiveness of MIA PaCa-2 pancreatic cancer cells.

OBJECTIVE: To analyze the capacity of neurotrophic artemin to promote the motility and invasiveness of MIA PaCa-2 pancreatic cancer cells. METHODS: MIA PaCa-2 was cultured in vitro and studied using transwell chambers for motility and invasiveness on treatment with different concentrations of aArtemin or its receptor GFRα3 were also determined. Expression of matrix metalloproteinase-2 (MMP-2) and epithelial cadherin (E-cadherin) was quantified using RT-PCR and Western blotting. RESULTS: MIA PaCa-2 pancreatic cancer cell motility and invasiveness was significantly increased with artemin and its receptor GFRα3 with dose dependence (P<0.01). MMP-2 production was also significantly increased (t=6.35, t=7.32), while E-cadherin was significantly lowered (t=4.27, t=5.61) (P<0.01). CONCLUSION: Artemin and its receptor GFRα3 can promote pancreatic cancer cell motility and invasiveness and contribute to aggressive behavior. The mechanism may be related to increased expression of MMP-2 molecule and down-regulation of E-cadherin expression.

[Identification of gastric cancer-related genes by multiple high throughput analysis and data mining].

OBJECTIVE: To investigate gastric cancer-related genes by combined multiple high throughput analysis and data mining, and to further identify gene markers that may be useful in the diagnosis and treatment of gastric cancer. METHODS: Data of expressed sequence tags (EST) and serial analysis of gene expression (SAGE) in Cancer Genome Anatomy Project (CGAP) were employed to analyze differential gene expression between normal and cancerous gastric epithelium,the obtained genes were further analyzed by virtual Northern blotting and compared with microarray data from Stanford Microarray Database (SMD). RESULTS: NCBI digital differential display (DDD), cDNA digital gene expression displayed (DGED) and SAGE DGED produced 165,286 and 181 differential expression genes.All these genes were analyzed by virtual Northern blotting and 45 genes were obtained. Comparing with microarray data, candidate genes were reduced to 12. Further RT-PCR analyses validated 4 genes, including ANXA1, MSMB, ANXA10 and PSCA, were differentially expressed in normal and cancerous gastric tissues. CONCLUSIONS: Combined multiple high throughput analysis and data mining is an effective strategy for identification of gastric cancer-related genes. Further analyses of these genes from data mining will provide biomarkers for the diagnosis and treatment of gastric cancer.