Respective roles of the mitogen-activated protein kinase (MAPK) family members in pancreatic stellate cell activation induced by transforming growth factor-ß1 (TGF-ß1).

Activated pancreatic stellate cells (PSCs) play a crucial role in the progression of pancreatic fibrosis. Transforming growth factor-ß (TGF-ß) is one of the strongest stimulator inducing fibrosis. The mitogen-activated protein kinase (MAPK) proteins (including ERK, JNK and p38 MAPK) are known to contribute to PSC activation and pancreatic fibrosis. Previous studies have identified PSC activation induced by TGF-ß1 is related to MAPK pathway, but the respective role of MAPK family members in PSC activation still unclear, and which family member may be the key mediator in mice PSC activation still controversial. In this study, we investigated the influence of different MAPK family member (JNK, ERK, and p38 MAPK) on mice PSC activation using an in vivo and in vitro model. The results showed p-JNK, p-ERK and p-p38 MAPK were all over-expressed in CP group, and p-JNK, p-ERK, and p-p38 MAPK were co-expressed with activated PSC. In vitro, TGF-ß1 induced JNK and ERK over-expression in PSCs. In contrast, p38 MAPK expression in PSC showed only a very weak increase. JNK- and ERK-specific inhibitors inhibited FN and α-SMA mRNA expression in PSCs, and a p38 MAPK inhibitor had no effect on PSC activation. These findings indicate that JNK and ERK were directly involved in the PSCs activation induced by TGF-ß1 and the development of pancreatic fibrosis. p38 MAPK participate in the progression of CP, but it does not respond to TGF-ß1 directly and may not be regarded as the target of TGF-ß1 induced PSC activation.

Three-dimensional conformal radiotherapy in combination with transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma.

PURPOSE: This study aimed to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) in combination with three-dimensional conformal radiotherapy (3D-CRT) in the treatment for locally advanced unresectable hepatocellular carcinoma (HCC). METHODS: From March 2000 to March 2009 a total of 158 patients with unresectable HCC treated and followed at our hospital were divided into TACE group (N=80) and TACE combined with 3D-CRT group (N=78). The TACE group was treated 3-6 times. In the combination group, 2-3 TACE courses were administered and 3D-CRT was performed 2 weeks after the last TACE. Three months after the end of treatment, imaging and serum AFP were carried out to assess the treatment efficacy. RESULTS: The response rates of TACE and the combination groups were 53.7% (43/80) and 71.8% (58/78) (p<0.05). The 1, 2, and 3-year survival rates of patients in the TACE and combination groups were 58.75, 36.25, 16.25%, and 78.48, 55.12 and 25.64% (p<0.05), respectively. Treatment compliance was good, with at least 2 TACE administrations for each case and at least 52 Gy for radiotherapy. In the TACE and the combination group, there were 2 and 3 cases with grade III/IV toxicity, respectively, without treatment-related death. CONCLUSION: 3D-CRT in combination with TACE significantly improve the therapeutic outcome in patients with locally advanced unresectable HCC, without creating severe toxicity.

Identification of the popliteal sciatic nerve through the above-knee lateral approach provides superior echogenicity and ultrasound visibility: a patient volunteer trial.

BACKGROUND: Distinguishing light-echoed nerves from surrounding structures is challenging but may be important in nerve block administration. We evaluated the effect of patient characteristics on the echogenicity or visibility of the popliteal sciatic nerve (PSN). METHODS: This study included adult patients who presented to the operating room as volunteers. The primary outcome was the success rate of nerve identification by ultrasound using different PSN access paths. The secondary outcome included the PSN visibility score (VIS), scan time, and PSN depth. Logistic regression analysis was used to identify factors associated with the PSN identification success rate. The Body Mass Index (BMI) proximal-based cut-off was used to compare the PSN identification success rate through different access paths. RESULTS: The PSN was successfully identified in 89.7% of the volunteers. The access paths (P<0.01) and BMI (P=0.01) were identified as independent predictors of successful PSN identification. A higher PSN identification success rate (P=0.01), a higher VIS (P<0.01), a more superficial PSN depth (P<0.01), and a shorter scan time (P<0.01) were observed in the above-knee lateral approach. Among volunteers with BMI≥26.77 kg/m2, the PSN identification success rate through the above-knee lateral approach was significantly higher (P<0.01), and PSN depth was shallower (P<0.01) than through the medial approach. CONCLUSIONS: The ultrasound-guided above-knee lateral approach for PSN block improved the PSN identification success rate, ensured a more superficial nerve location, and provided a clearer image.

Remifentanil injected during analepsia shortens length of postanesthesia care unit stay in patients undergoing laparoscopic surgery for endometrial cancer: a randomized controlled trial.

BACKGROUND: To guarantee efficient operating room (OR) activity, tracheal extubation is often performed in the postanesthesia care unit (PACU). Therefore, the ability of PACU to accommodate postoperative patients is crucial. Optimizing extubation management may speed up the turnover of PACU beds. The aim of the present study was to investigate the effect of remifentanil, which is used during analepsia, on the length of PACU stay in patients undergoing laparoscopic surgery for endometrial cancer. METHODS: In this prospective trial, we recruited a total of 99 patients, who were scheduled for laparoscopic surgery for endometrial cancer. At the end of the surgery, all patients were immediately transferred to the PACU and continued mechanical ventilation. Upon PACU admission, sputum aspiration was routinely performed. If the hemodynamic parameters fluctuated >30% of the baseline level, or patients moved unconsciously without reaching the criteria of extubation, a bolus injection of either 1 µg/kg remifentanil (Rem group, n=51) or propofol 1.0 mg/kg (Pro group, n=48) was randomly administered. The primary outcome was the duration of PACU stay. The secondary outcomes included time to respiratory breath recovery and time to extubation, along with bispectral index (BIS) values and hemodynamic status after remifentanil or propofol intervention. Times of repeated intervention, rescue administration of vasoactive drugs, and the incidence of adverse events were recorded. Visual analog scale and satisfaction scores at the time of PACU discharge were also evaluated. RESULTS: The duration of PACU stay was shorter in the Rem group than in the Pro group [49 (46.47-51.06 minutes) vs. 62 minutes (60.75-69.29 minutes), P<0.0001]. Compared with the Pro group, the time to spontaneous breathing recovery, the time to extubation, and the incidence of hypoxemia after extubation were reduced in the Rem group (P<0.0001, P<0.0001, P=0.03, respectively). After anesthetic administration, the BIS value decreased less in the Rem group (P<0.0001); blood pressure and heart rate (HR) declined, but were comparable in both groups. CONCLUSIONS: Remifentanil, which is injected during analepsia, significantly shortens the duration of PACU stay without increasing adverse events in the peri-extubation period.

Efficacy and safety of ultrasound-guided above-knee lateral approach for popliteal sciatic nerve block in surgeries below the knee: a randomized controlled trial.

BACKGROUND: Ultrasound guidance has become a standard method for detection of nerve structures in regional anesthesia. During ultrasound-guided blockade, to identify anatomical structures is crucial but can be challenging. In clinical practice, we find a wide difference in the visibility score of the sciatic nerve (SN) through different approaches. This study aimed to compare SNB through the anterior and above-knee lateral approach in terms of identification ease, performance efficacy, and safety. METHODS: Patients scheduled for below-knee surgery were randomized to either receive SNB using the above-knee lateral approach (Group L, n=27) or the anterior approach (Group A, n=26). The primary outcome was the visibility score of SN. Secondary outcomes included the time taken to identify the SN, nerve depth, success rate of SN identification, number of needle passes, time to elicit foot flexion, needle depth, and occurrence of SNB complications. Additionally, the sensory block onset and analgesia duration were assessed. RESULTS: We included 53 adult patients. Compared with Group A, Group L showed a higher SN visibility score [3.25 (3.17, 3.67) vs. 2.50 (1.86, 2.68), P<0.001]. The scan time was significantly shorter in Group L [8.70 (6.01) s vs. 31.54 (11.87) s, P<0.001]. The depth of the SN was 3.20 (0.56) cm in Group L and 5.53 (0.84) cm in Group A (P<0.001), and the needle insertion depth was 7.15 (0.90) cm in group L and 8.32 (1.13) cm in Group A (P<0.001). The number of needle passes was less in Group L, as well as the time to elicit foot flexion, and the time taken to perform the SN block (all P<0.001). The success rate of SN identification was non-significantly higher in Group L. There was no significant between-group difference in the onset of sensory block, as well as postoperative analgesia duration. None of the approaches involved acute systemic toxicity and hematoma occurrence. CONCLUSIONS: Based on the visibility score, the above-knee lateral approach allowed easy SN identification and safe SNB. Using the ultrasound-guided above-knee lateral approach for SNB in below-knee surgeries could be a reliable choice.

Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis.

AIM: To explore the role of macrophages in chronic pancreatitis (CP) and the effect of Dachaihu decoction (DCHD) on pancreatic fibrosis in mice. METHODS: KunMing mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine (3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6 (IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas. RESULTS: Compared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α mRNA, and fibronectin levels were reduced. CONCLUSION: The dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.

Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice.

AIM: To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis. METHODS: The mice were randomly divided into 2 groups (n = 50), control group and model group. The mice in model group were given ethanol (10%) in drinking water after injection of dibutyltin dichloride (DBTC) (8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein (60% ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin (FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen type I (COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA in the pancreas was assessed by real time PCR. RESULTS: DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group (P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 mRNA in pancreas decreased, but TIMP-1 mRNA increased at model group. CONCLUSION: DBTC joint Ethanol drinking can induce chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and handy experimental method. The model is suitable to study the mechanism of pancreatic fibrosis in chronic pancreatitis.

Phase II clinical study on the GEMOX regimen as second- line therapy for advanced ovarian cancer.

AIM: To investigate the effectiveness and adverse effects of gemcitabine by fixed-dose rate infusion plus oxaliplatin (GEMOX regimen) as second-line therapy for advanced ovarian cancer. METHODS: 64 patients with advanced ovarian cancer were divided into an experimental group (44 cases) and a control group (20 cases). The experimental group was treated with continuous intravenous infusion of gemcitabine at 1000 mg/m(2) with a fixed-dose rate of 10 mg/m(2)/min, on days 1 and 8 and oxaliplatin at 100 mg/m(2) on day 1, IVGTT, repeated every 3 weeks. The control group was treated with intravenous infusion of gemcitabine at 1000 mg/m(2) within 30 min on days 1 and and oxaliplatin at 100 mg/m(2) on day 1, IVGTT, again repeated every 3 weeks. CT scans or MRI were used for review every 1-2 cycles. RESULTS: The effective rate in the experimental group was significantly high than control group (43.2% vs 35.0%; P < 0.05), with no obvious difference of hematologic or non-hematologic toxicity between the two groups (P > 0.05). CONCLUSION: GEMOX regimen is very effective to treat advanced ovarian cancer, with low toxicity, good tolerance and improved life quality in patients.

Effects of monoclonal antibodies against human stathmin combined with paclitaxel on proliferation of the QG-56 human lung carcinoma cell line.

OBJECTIVE: To explore whether monoclonal antibodies against stathmin and the chemotherapuetic agent paclitaxel have synergenic effects in inhibiting growth and inducing apoptosis in human QG-56 cells. METHODS: QG-56 cells were treated with monoclonal antibodies against stathmin or paclitaxel alone or in combination, with untreated cells used as controls. After 24, 48, 72 and 96 hours the cell growth condition was observed under an inverted microscope and inhibition was studied by MTT assay; apoptosis was analyzed by flow cytometry. RESULTS: The populations decreased and cell shape and size changed after the various treatments. Monoclonal antibodies against stathmin and paclitaxel used alone or incombination inhibited the proliferation of QG-56 cells, especially in combination with synergism (P<0.05). Combined treatment also resulted in a significantly higher apoptosis rate than in the other groups (P<0.05). CONCLUSIONS: Monoclonal antibodies against stathmin and paclitaxel used alone or in combination can inhibit proliferation of QG-56 cells and induce apoptosis when applied together, The observed synergistic effects may have important implications for clinical application.

Expression of ß-tubulin III and survivin in advance stage breast cancer correlates with chemotherapeutic effects of docetaxel.

AIMS: To investigate the relationship between the expression of ß-tubulin III and survivin in advanced breast cancers and chemotherapeutic effects of docetaxel. METHODS: Clinical pathological data of 74 patients with advanced breast cancer were retrospectively analyzed after docetaxel chemotherapy. Expression of ß-tubulin III and survivin was assessed by immunohistochemistry and analyzed with reference to therapeutical and adverse effects of docetaxel. RESULTS: The positive expression rate of ß-tubulin III was 38.1% (32/84), while that of survivin was 76.2% (64/84). The effective rate (complete response + partial response) was 52.4%. That for patients with the positive expression of ß-tubulin III or/and survivin was significantly lower than for those with negative expression (P<0.05). There were significant differences in the non-progression of median diseases, 1-year and 2-year survival rates of between the patients with positive and negative expression (P<0.05). The main side effects were myelosuppression, alimentary canal response and alopecia, no differences being observed between groups. CONCLUSIONS: The combined detection of ß-tubulin III and survivin is a predictive index for chemotherapy effects of docetaxel in metastatic breast cancer.