Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking.

BACKGROUND: Tactile and mechanical pain are crucial to our interaction with the environment, yet the underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) is an evolutionarily conserved protein that is documented in the endocytosis pathway. However, the role of EndoA2 in the regulation of mechanical sensitivity and its underlying mechanisms are currently unclear. METHODS: Male and female C57BL/6 mice (8-12 weeks) and male cynomolgus monkeys (7-10 years old) were used in our experiments. Nerve injury-, inflammatory-, and chemotherapy-induced pathological pain models were established for this study. Behavioral tests of touch, mechanical pain, heat pain, and cold pain were performed in mice and nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation and patch-clamp recordings were performed to gain insight into the mechanisms. RESULTS: The results showed that EndoA2 was primarily distributed in neurofilament-200-positive (NF200+) medium-to-large diameter dorsal root ganglion (DRG) neurons of mice and humans. Loss of EndoA2 in mouse NF200+ DRG neurons selectively impaired the tactile and mechanical allodynia. Furthermore, EndoA2 interacted with the mechanically sensitive ion channel Piezo2 and promoted the membrane trafficking of Piezo2 in DRG neurons. Moreover, as an adaptor protein, EndoA2 also bound to kinesin family member 5B (KIF5B), which was involved in the EndoA2-mediated membrane trafficking process of Piezo2. Loss of EndoA2 in mouse DRG neurons damaged Piezo2-mediated rapidly adapting mechanically activated currents, and re-expression of EndoA2 rescued the MA currents. In addition, interference with EndoA2 also suppressed touch sensitivity and mechanical hypersensitivity in nonhuman primates. CONCLUSIONS: Our data reveal that the KIF5B/EndoA2/Piezo2 complex is essential for Piezo2 trafficking and for sustaining transmission of touch and mechanical hypersensitivity signals. EndoA2 regulates touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking in sensory neurons. Our findings identify a potential new target for the treatment of mechanical pain.

More Liver Metastases Detected Intraoperatively Indicates Worse Prognosis for Colorectal Liver Metastases Patients after Resection Combined with Microwave Ablation.

Background: Whether more tumor numbers detected in surgery compared to preoperative image affecting survival of colorectal liver metastases (CRLM) patients after hepatectomy combined with microwave ablation (MWA) remains unclear. Methods: From 2013 to 2018, 85 CRLM patients who underwent hepatectomy combined with MWA were retrospectively assessed. Compared to the tumor numbers in preoperative image, patients with equal intraoperative tumor numbers were defined as the equal number group (n = 45); patients detected more tumor numbers in surgery were defined as the more number group (n = 40). Clinicopathological factors and prognosis were compared between two groups. Results: Compared to the equal number group, the more number group was characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5 (all P < 0.05). Median survival time was 46.7 months and 26.8 months in the equal and more number group. Significantly worse overall survival (OS) was found in more number group to the equal number group (P = 0.027). In Cox analysis, more tumor number than image and high level of carbohydrate antigen 19-9 (CA19-9) were poor prognostic factors for OS. Conclusion: In patients receiving hepatectomy combined with MWA, detecting more liver metastases in surgery than preoperative image indicates poor long-term survival. These patients were characterized by more lymphatic metastasis, synchronous metastasis of liver lesion, and tumor numbers over 5. Intensive follow-up to detect early recurrence and potent postoperative therapy to improve survival may be justified in patients detected more tumor numbers in surgery with a high CA19-9 level.

Learning curve of robotic portal lobectomy for pulmonary neoplasms: A prospective observational study.

BACKGROUND: We aim to assess the learning curve of robotic portal lobectomy with four arms (RPL-4) in patients with pulmonary neoplasms using prospectively collected data. METHODS: Data from 100 consecutive cases with lung neoplasms undergoing RPL-4 were prospectively accumulated into a database between June 2018 and August 2019. The Da Vinci Si system was used to perform RPL-4. Regression curves of cumulative sum analysis (CUSUM) and risk-adjusted CUSUM (RA-CUSUM) were fit to identify different phases of the learning curve. Clinical indicators and patient characteristics were compared between different phases. RESULTS: The mean operative time, console time, and docking time for the entire cohort were 130.6 ± 53.8, 95.5 ± 52.3, and 6.4 ± 3.0 min, respectively. Based on CUSUM analysis of console time, the surgical experience can be divided into three different phases: 1-10 cases (learning phase), 11-51 cases (plateau phase), and >51 cases (mastery phase). RA-CUSUM analysis revealed that experience based on 56 cases was required to truly master this technique. Total operative time (p < 0.001), console time (p < 0.001), and docking time (p = 0.026) were reduced as experience increased. However, other indicators were not significantly different among these three phases. CONCLUSIONS: The RPL-4 learning curve can be divided into three phases. Ten cases were required to pass the learning curve, but the mastery of RPL-4 for satisfactory surgical outcomes requires experience with at least 56 cases.

ATF4 selectively regulates heat nociception and contributes to kinesin-mediated TRPM3 trafficking.

Effective treatments for patients suffering from heat hypersensitivity are lacking, mostly due to our limited understanding of the pathogenic mechanisms underlying this disorder. In the nervous system, activating transcription factor 4 (ATF4) is involved in the regulation of synaptic plasticity and memory formation. Here, we show that ATF4 plays an important role in heat nociception. Indeed, loss of ATF4 in mouse dorsal root ganglion (DRG) neurons selectively impairs heat sensitivity. Mechanistically, we show that ATF4 interacts with transient receptor potential cation channel subfamily M member-3 (TRPM3) and mediates the membrane trafficking of TRPM3 in DRG neurons in response to heat. Loss of ATF4 also significantly decreases the current and KIF17-mediated trafficking of TRPM3, suggesting that the KIF17/ATF4/TRPM3 complex is required for the neuronal response to heat stimuli. Our findings unveil the non-transcriptional role of ATF4 in the response to heat stimuli in DRG neurons.

Foxo1 selectively regulates static mechanical pain by interacting with Nav1.7.

ABSTRACT: Mechanical allodynia is a debilitating condition for millions of patients with chronic pain. Mechanical allodynia can manifest in distinct forms, including brush-evoked dynamic and filament-evoked static allodynia. In the nervous system, the forkhead protein Foxo1 plays a critical role in neuronal structures and functions. However, the role of Foxo1 in the somatosensory signal remains unclear. Here, we found that Foxo1 selectively regulated static mechanical pain. Foxo1 knockdown decreased sensitivity to static mechanical stimuli in normal rats and attenuated static mechanical allodynia in rat models for neuropathic, inflammatory, and chemotherapy pain. Conversely, Foxo1 overexpression selectively enhanced sensitivity to static mechanical stimuli and provoked static mechanical allodynia. Furthermore, Foxo1 interacted with voltage-gated sodium Nav1.7 channels and increased the Nav1.7 current density by accelerating activation rather than by changing the expression of Nav1.7 in dorsal root ganglia neurons. In addition, the serum level of Foxo1 was found to be increased in chronic pain patients and to be positively correlated with the severity of chronic pain. Altogether, our findings suggest that serum Foxo1 level could be used as a biological marker for prediction and diagnosis of chronic pain. Moreover, selective blockade of Foxo1/Nav1.7 interaction may offer a new therapeutic approach in patients with mechanical pain.

Effects of Anesthetic Technique on Postoperative Pulmonary Metastasis in Patients Undergoing Laryngectomy.

BACKGROUND: Whether laryngeal cancer is directly implanted into the lungs during orotracheal intubation is still unclear. Therefore, this study aimed to find whether orotracheal intubation is an independent risk factor for postoperative pulmonary metastasis in patients undergoing laryngectomy. PATIENTS AND METHODS: Medical records from January 1, 2006, to December 31, 2016, were reviewed. According to similar propensity scores, patients who received orotracheal intubation (tracheal intubation group, n = 515) were matched 1:1 with those who received tracheotomy (tracheotomy group, n = 326) in the induction of general anesthesia. The primary outcome was postoperative pulmonary metastasis. Secondary outcomes included local recurrence, lymphatic metastasis, tracheostomal recurrence and overall survival. RESULTS: Between the two groups, there was no significant difference in postoperative pulmonary metastasis (P = 0.688), local recurrence (P = 0.215), lymphatic metastasis (P = 0.480), tracheostomal recurrence (P = 0.246) or all-cause death (P = 0.299). The primary site of cancer was an independent risk factor for pulmonary metastasis [HR 0.29, 95% CI 0.13-0.68; P = 0.013] and local recurrence (HR 2.69, 95% CI 1.39-5.21; P = 0.003). Type of surgery (HR 3.13, 95% CI 2.03-4.84; P < 0.001) and N classification of TNM (HR 0.27, 95% CI 0.10-0.75; P = 0.012) were risk factors for local recurrence. Postoperative chemotherapy was an independent risk factor for lung metastasis (HR 7.58, 95% CI 3.11-18.47; P < 0.001) and lymphatic metastasis (HR 5.18, 95% CI 2.57-11.91; P < 0.001), and 5-year overall survival was associated with age (P = 0.028), clinical stage (P < 0.001) and postoperative chemotherapy (P = 0.003) but not with anesthetic technique (P = 0.473). CONCLUSION: This retrospective study suggests that orotracheal intubation in laryngectomy is not a risk factor for postoperative pulmonary metastasis, local recurrence, lymphatic metastasis or overall survival.

Intention to control low central venous pressure reduced blood loss during laparoscopic hepatectomy: A double-blind randomized clinical trial.

BACKGROUND: Excessive intraoperative hemorrhage is a critical factor of poor prognoses after hepatectomy. Low central venous pressure during parenchymal transection is recognized to effectively reduce intraoperative hemorrhage in open procedures. However, the role of controlled low central venous pressure in laparoscopic hepatectomy is still controversial. METHODS: In the present randomized clinical trial, we set up a standard boundary of low central venous pressure according to our Pilot Study, then enrolled patients scheduled for elective laparoscopic hepatectomy and allocated them randomly to a group undergoing central venous pressure reduction by anesthesiologic interventions or a control group. The primary efficacy endpoint was total intraoperative blood loss and perioperative adverse events. Analyses were performed following the intention-to-treat principle, and patients and surgeons were blinded (ClinicalTrials.gov, Number: NCT03422913). RESULTS: Between January 2017 and October 2018, 146 out of 469 patients were randomized and eligible for inclusion in the final analyses. Based on the retrospective training cohort, we set a central venous pressure of 5 cm H2O as a cutoff value (standard low central venous pressure). Compared with patients in the control group, those in the controlled low central venous pressure group had a significantly lower central venous pressure during resection (4.83 ± 3.41 cm H2O vs 9.26 ± 3.38 cm H2O; P < .001) and significantly reduced total intraoperative blood loss (188.00 ± 162.00 mL vs 346.00 ± 336.00 mL; P < .001). The perioperative adverse events were comparable in both study groups (P = .313). CONCLUSION: The safety and efficacy of controlled low central venous pressure were demonstrated in complex laparoscopic hepatectomy for the first time by our study, and this technique is recommended to be applied routinely in laparoscopic hepatectomy.

Sevoflurane promotes migration, invasion, and colony-forming ability of human glioblastoma cells possibly via increasing the expression of cell surface protein 44.

Surgical resection of primary solid tumor under anesthesia remains a common practice. It has been concerned whether general anesthetics, especially volatile anesthetics, may promote the growth, migration, and invasion of cancer cells. In this study, we examined the effects of sevoflurane on human glioblastoma cells and determined the role of cluster of differentiation (CD) 44, a cell surface protein involved in cell growth, migration, and invasion, in sevoflurane's effects. We showed that exposure to 1%-4% sevoflurane did not change the cell proliferation, but concentration-dependently increased the invasion of human glioblastoma U251 cells. Furthermore, 4% sevoflurane significantly increased the migration and colony-forming ability of U251 cells. Similar results were observed in human glioblastoma A172 cells. Exposure to sevoflurane concentration-dependently increased the activity of calpains, a group of cysteine proteinases, and CD44 protein in U251 and A172 cells. Knockdown of CD44 with siRNA abolished sevoflurane-induced increases in calpain activity, migration, invasion, and colony-forming ability of U251 cells. Inhalation of 4% sevoflurane significantly increased the tumor volume and invasion/migration distance of U87 cells from the tumor mass in the nude mice bearing human glioblastoma U87 xenograft in the brain. The aggravation by sevoflurane was attenuated by CD44 silencing. In conclusion, sevoflurane increases the migration, invasion, and colony-forming ability of human glioblastoma cells in vitro, and their tumor volume and invasion/migration in vivo. Sevoflurane enhances these cancer cell biology features via increasing the expression of CD44.

The incidence and distribution of mediastinal lymph node metastasis and its impact on survival in patients with non-small-cell lung cancers 3 cm or less: data from 2292 cases.

OBJECTIVES: Our goal was to investigate the incidence and distribution of mediastinal lymph node metastases (MLNM) in non-small-cell lung cancers (NSCLC) 3 cm or less, with the purpose of guiding mediastinal lymph node dissection. METHODS: A total of 2292 cases seen between January 2001 and December 2014 were included. These patients were grouped according to the lobes with the primary tumours. The incidence and distribution of pathological MLNM were compared among the groups. The impact of MLNM on overall survival was also compared. RESULTS: The most common mediastinal metastatic sites for different primary tumour lobes were as follows: right upper lobe, 17.7% (87/492) for level 4R; right middle lobe, 14.9% (28/188) for level 7; right lower lobe, 19.8% (82/414) for level 7; left upper lobe, 18.2% (96/528) for level 5; and left lower lobe, 16.6% (42/253) for level 7. For patients with tumours in the upper lobe, the median survival time was 32 months for those with MLNM in the subcarinal zone or lower zone compared with 83 months for those with MLNM only in the upper zone (P < 0.01). When the tumours were 1 cm or less, the incidence of MLNM to the lower zone for upper lobe tumours and of MLNM to the upper zone for lower lobe tumours was zero. CONCLUSIONS: Different primary NSCLC lobe locations have a different propensity to be sites of MLNM for those tumours that are 3 cm or less. For tumours no larger than 1 cm, a lower zone mediastinal lymph node dissection might be unnecessary for upper lobe tumours and an upper zone mediastinal lymph node dissection might be unnecessary for lower lobe tumours.

Puerarin Relieves Paclitaxel-Induced Neuropathic Pain: The Role of Nav1.8 ß1 Subunit of Sensory Neurons.

Currently there is no effective treatment available for clinical patients suffering from neuropathic pain induced by chemotherapy paclitaxel. Puerarin is a major isoflavonoid extracted from the Chinese medical herb kudzu root, which has been used for treatment of cardiovascular disorders and brain injury. Here, we found that puerarin dose-dependently alleviated paclitaxel-induced neuropathic pain. At the same time, puerarin preferentially reduced the excitability and blocked the voltage-gated sodium (Nav) channels of dorsal root ganglion (DRG) neurons from paclitaxel-induced neuropathic pain rats. Furthermore, puerarin was a more potent blocker of tetrodotoxin-resistant (TTX-R) Nav channels than of tetrodotoxin-sensitive (TTX-S) Nav channels in chronic pain rats' DRG neurons. In addition, puerarin had a stronger blocking effect on Nav1.8 channels in DRG neurons of neuropathic pain rats and ß1 subunit siRNA can abolish this selective blocking effect on Nav1.8. Together, these results suggested that puerarin may preferentially block ß1 subunit of Nav1.8 in sensory neurons contributed to its anti-paclitaxel induced neuropathic pain effect.

Expression and clinical value of programmed cell death-ligand 1 (PD-L1) in diffuse large B cell lymphoma: a retrospective study.

BACKGROUND: The programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis. METHODS: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical (IHC) assay. The expression of anaplastic lymphoma kinase (ALK), CD5, CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus (EBV)-encoded RNAs (EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis. RESULTS: Of the 204 patients, 100 (49.0%) were PD-L1-positive in tumor cells and 44 (21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype (P = 0.02 and P = 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment (P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression (r = - 0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival (OS) rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells (P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS (P < 0.01). CONCLUSIONS: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.

Complete mediastinal lymph node dissection in video-assisted thoracoscopic lobectomy versus lobectomy by thoracotomy.

BACKGROUND: Although video-assisted thoracic surgery (VATS) lobectomy has been used more and more frequently for the treatment of patients with early-stage lung cancer, controversies are mainly focused on whether the complete mediastinal lymph node dissection (MLND) can be achieved by VATS. This retrospective study aimed to compare the validity of MLND between VATS and open thoracotomy. METHODS: Patients with lung cancer were matched from a pool of pulmonary lobectomies performed by one surgeon. Patients undergoing VATS were matched with those undergoing thoracotomy in terms of gender, age, clinical tumor stage, tumor location, and surgical procedure. RESULTS: After matching, 31 patients in VATS group and 31 patients in open group were eligible for analysis. In the VATS and open groups, the mean total number of dissected lymph nodes was 28.2 ± 8.4 and 29.8 ± 11.6 (p = 0.517), respectively. In the VATS and open groups, the number of N1 nodes was 9.5 ± 4.1 and 8.4 ± 4.7 (p = 0.333), respectively. And the number of N2 nodes was also similar between the VATS and open group (18.6 ± 7.0 vs 21.4 ± 10.0, p = 0.211). No significant differences were observed between the two groups in the operating time, the blood loss, the length of chest tube drainage, the length of hospital stay, and the rate of specific complications. CONCLUSION: Our early experience suggests that, with regard to the number of the dissected lymph nodes, VATS lobectomy can achieve complete MLND, compared with the traditional approach. MLND by VATS is technically feasible and safe for early-stage lung cancer.

Heart fatty acid-binding protein may not be an early biomarker for anthracycline-induced cardiotoxicity in rabbits.

The objective of this study was to investigate the feasibility of using serum heart fatty acid-binding protein (H-FABP) concentrations as an early biomarker for doxorubicin-induced myocardial damage. Forty-four male rabbits were randomly divided into a control (8 rabbits) or one of four doxorubicin groups (8 rabbits in each group). Rabbits in the control group received saline, whereas rabbits in the doxorubicin group received 2 mg/kg doxorubicin weekly for 1-8 weeks. Rabbits in the doxorubicin groups received doxorubicin 2 mg/kg for one (Group 1, 8 rabbits), two (Group 2, 8 rabbits), four (Group 3, 9 rabbits), or eight (Group 4, 11 rabbits) weeks. Echocardiography was performed to measure left ventricular ejection fraction (LVEF), shortening fraction (FS), and E/A ratio. Cardiotoxicity scores were assessed by light microscopy using Billingham's method and also by electron microscopy. Serum H-FABP concentrations were quantified by a rabbit-specific enzyme-linked immunosorbent assay. Decreased LVEF, FS, and E/A ratio were detected in Group 4 (P < 0.05). Billingham cardiomyopathy scores of the rabbits in Group 3 were significantly higher (P < 0.05) than those of rabbits in the control group or Groups 1 or 2. Billingham cardiomyopathy scores in Group 4 were the highest of all groups (P < 0.05). Myocardial injury was demonstrable by electron microscopy in rabbits in Groups 2, 3, and 4. Compared with the control group, serum H-FABP concentrations increased only in Group 4 (P < 0.05). Serum H-FABP concentrations may not be a sensitive method for assessing early cardiotoxicity of doxorubicin.

[Application of a narcotrend-assisted anesthesia in-depth monitor in the microwave coagulation for liver cancer during total intravenous anesthesia with propofol and fentanyl].

BACKGROUND AND OBJECTIVE: CT-guided microwave coagulation is a minimally invasive surgery for patients with liver cancer. Total intravenous anesthesia with propofol and fentanyl is commonly used. The depth of anesthesia during microwave coagulation for liver cancer is still monitored by clinical signs. There are few subjective and effective indicators. This study explored the application of Narcotrend-assisted "depth of anesthesia" monitoring on microwave coagulation for patients with liver cancer during total intravenous anesthesia with propofol and fentanyl. METHODS: Forty liver cancer patients underwent CT-guided microwave coagulation were randomly assigned to receive Narcotrend index monitoring or standard clinical monitoring for depth of anesthesia with 20 patients in each group. All patients received total intravenous anesthesia with propofol and fentanyl. The depth of anesthesia for patients in the Narcotrend group was measured according to a Narcotrend index, which was maintained between D2 and E0. The depth of anesthesia for those in the standard clinical practice group was measured according to heart rate, mean arterial pressure, and patient movement. Changes of hemodynamics, the duration of the emergence from anesthesia, and the recovery of orientation were recorded. The doses of propofol and fentanyl, postoperative visual analogue scores (VAS), and the incidence of postoperative nausea and vomiting were also recorded. RESULTS: There was no significant alteration in heart rate or mean arterial pressure between the two groups. Compared with other anesthetic stages, both heart rate and mean arterial pressure decreased during the induction of the anesthesia in the two groups(P<0.05). The doses of propofol were higher in the standard clinical practice group than in the Narcotrend group [(460+/-30) mg vs. (380+/-35) mg, P<0.01]. The duration of emergence and orientation were longer in the standard clinical practice group than in the Narcotrend group [(9.5+/-2.9) min vs. (4.9+/-2.2) min, P<0.01; (12.2+/-3.5) min vs. (6.6+/-3.2) min, P<0.01, respectively]. There was no difference in the dosage of fentanyl, VAS, or the incidence of postoperative nausea or vomiting between the two groups (P>0.05). CONCLUSION: For patients with liver cancer, monitoring the depth of anesthesia with Narcotrend on microwave coagulation can contribute to lower dosage of propofol and shorten duration of recovery during total intravenous anesthesia with propofol and fentanyl.

[Effects of neuraxial block and general anesthesia on tumor metastasis in rats].

OBJECTIVE: To investigate the effects of different anesthesia methods on immune surveillance and tumor metastasis in tumor-bearing rats. METHODS: Seventy-two Fischer 344 rats were randomly assigned into 3 equal groups and anesthetized for 1 h with ketamine (group K), propofol (group P), or neuraxial block (group B). All the rats were subjected to laparotomy followed by intravenous injection of MADB106 tumor cells, and 24 h after the injection, the number and activity of circulating CD3(+), CD4(+), CD8(+), and D4(+)/CD8(+) lymphocyte subsets and NK cellèCD161a(+)éwere assessed. Three weeks later, the lung metastases were counted. RESULTS: Compared with those in group B, the numbers of CD3(+), CD4(+), CD8(+), and CD161a(+) lymphocytes and the activity of circulating NK cells were significantly reduced, and the lung metastases of MADB106 increased significantly in groups K and P (P<0.05 or 0.01 ). The activity of immune surveillance in group K was significantly lower than that in group P except for CD8(+) cells, and the tumor metastases in group K increased significantly in comparison with those in group P (P<0.05 or 0.01). CONCLUSION: Neuraxial block provides protection of the activity of immune surveillance and reduces tumor metastases in tumor-bearing rats compared with general anesthesia.

[Correlation of acute pain treatment to occurrence of chronic pain in tumor patients after thoracotomy].

BACKGROUND & OBJECTIVE: Some researches found that the intensity, property and management of acute pain are associated with chronic pain in tumor patients after thoracotomy. Chronic pain may be transformed from acute pain. However, there are no routine or standard strategies to effectively prevent or relieve chronic pain in tumor patients after thoracotomy. This study was to explore the correlation of acute and chronic pain in tumor patients after thoracotomy. METHODS: A total of 105 patients (American Society of Anesthesiologists physical status I-II) underwent thoracotomy were randomly divided into 3 groups: 36 received administration of ropivacaine and morphine through thoracic epidural preoperatively (group PE), 36 received the same treatment postoperatively (group E), and 33 received intravenous infusion of fentanyl postoperatively (group IV). VAS scores were recorded in the first 48 h after operation. The occurrence of chronic pain was observed at the first, second, third, sixth months after operation. RESULTS: VAS scores in the first 48h after operation were significantly lower in group PE and group E than that in group IV (P<0.05). VAS scores were significantly lower in group PE than in group E (P=0.004 at 4 h, P=0.013 at 8 h, P=0.035 at 24 h). The occurrence rate of pain after operation was significantly lower in group PE than in groups E and IV in the first and second months (Chi2=5.989, P=0.014; Chi2=7.603, P=0.006), and lower in groups PE and E than in group IV in the third and sixth months (Chi2=6.585, P=0.010; Chi2=8.661, P=0.003). The duration of pain was significantly shorter in group PE than in groups E and IV (P=0.027, P=0.009). CONCLUSIONS: Chronic pain after thoracotomy is associated with the intensity and management of acute pain after thoracotomy. The patients with intensive acute pain would experience intensive and long-term chronic pain. Preemptive administration with thoracic epidural ropivacaine and morphine can decrease the incidence and duration of chronic pain after operation.

[Protective effect of ketamine against acute rat lung injury induced by liopolysaccharide and its mechanism].

OBJECTIVE: To investigate the protective effects of different concentrations of ketamine against acute lung injury induced by lipopolysaccharide (LPS) in rats and its mechanism. METHODS: Forty-eight male Wistar rats were randomized into 4 equal groups, namely the control group, LPS group, ketamine group I (5 mg/kg), and ketamine group II (10 mg/kg). The neutrophil count, protein contents in the bronchoalveolar lavage fluid (BALF) and the wet/dry lung weight ratio were measured 4 h after LPS injection. TNF-alpha, IL-8, NO, iNOS and NF-kappaB were also measured in the lung tissues. RESULTS: In LPS group, the neutrophil count, protein contents in BALF, the wet/dry lung weight ratio and the levels of tumor necrosis factor-alpha(TNF-alpha), interleukin-8 (IL-8), and NO were all significantly increased compared with the control group (P<0.01). The mRNA expression of iNOS and the protein expression of NF-kappaB were also increased in LPS groups. Ketamine treatment attenuated the increase in wet/dry lung weight ratio, neutrophil count, and protein contents in BALF in a dose-dependent manner. Ketamine also dose-dependently inhibited the production of TNF-alpha, IL-8 , and NO and lowered iNOS mRNA and NF-kappaB protein expression. CONCLUSION: Ketamine can offer protection against LPS-induced acute lung injury in rats by inhibiting the expression of NF-kappaB and attenuating the production of the inflammatory cytokines.

[Beneficial effects of metoprolol on perioperative cardiac function of elderly esophageal cancer patients].

BACKGROUND & OBJECTIVE: The elderly esophageal cancer patients undergoing esophagectomy are increasing now. How to protect their cardiac functions and reduce perioperative mortality and morbidity of cardiac events is an urgent problem to be solved. Prophylactic beta-blockers have been recently applied during surgery. This study was to evaluate the beneficial effects of metoprolol on perioperative cardiac function of elderly esophageal cancer patients. METHODS: The esophageal cancer patients, no less than 65 years old, scheduled for elective esophagectomy were enrolled, and randomized into metoprolol group and control group. The patients of metoprolol group received metoprolol to control heart rate from anesthesia induction to 72 h after operation. Perioperative hemodynamic data were recorded at time points of baseline, drug administration, 2 min after induction, intubation, 4 min after intubation, incision, thoracic exposure, 60 min after incision, 10 min before the completion of operation, the completion of operation, extubation, and 15 min after extubation. The serum level of cardiac troponin T (cTnT), the occurrence of perioperative cardiac events and postoperative sinus tachycardia were also recorded. RESULTS: Compared with preoperative values, systolic arterial pressure was significantly higher at intubation (P<0.05), heart rate was significantly faster at intubation and extubation (P<0.05) in control group; while the hemodynamic data had no obvious changes in metoprolol group (P>0.05). The serum level of cTnT was elevated in 3 patients of control group within 3 days after operation, and remained normal in all patients of metoprolol group (P=0.237); cardiac events occurred in 6 patients of control group (including 2 cases of myocardial ischemia and 4 cases of atrial fibrillation), but didn't occur in metoprolol group (P=0.024). No myocardial infarction and death occurred in the 2 groups during operation. The occurrence rate of tachycardia was significantly higher in control group than in metoprolol group (15 cases vs. 6 cases, P<0.05). CONCLUSION: Metoprolol can reduce the occurrence of perioperative cardiac events and postoperative tachycardia in the elderly esophageal cancer patients undergoing esophagectomy, and restrain the effects of tracheal intubation or extubation on heart rate and blood pressure.