Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

[Clinical value of routine contrast esophagram in the diagnosis of anastomotic leakage for three-incision esophagectomy with cervical anastomosis].

Objective: To examine the clinical value of routine contrast esophagram (RCE) for the diagnosis of anastomotic leakage (AL) after three-incision esophagectomy with cervical anastomosis. Methods: Clinical data of 1 022 patients with esophageal cancer who underwent McKeown three-incision esophagectomy with cervical anastomosis from January 2015 to December 2019 at Department of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Hospital and Institute were analyzed retrospectively. There were 876 males and 146 females, aging(M(IQR)) 48(16) years (range: 36 to 84 years). There were 253 patients (24.8%) with neoadjuvant therapy, and 817 patients (79.9%) with minimally invasive esophagectomy. According to the diagnosis and treatment habits of the attending surgeons, 333 patients were included in the RCE group, and RCE was performed on the 7th day postoperative, while 689 patients were included in the non-RCE group, and RCE was performed when the patients had suspicious symptoms. Taking clinical symptoms, RCE, CT, endoscopy and other methods as reference to the diagnosis of AL, the sensitivity and specificity were used to analyze and evaluate the efficacy of RCE for the diagnosis of AL. The data were compared by U test or χ² test between groups. Results: The incidence rate of AL after three-incision esophagectomy was 7.34% (75/1 022), including 30 cases in the RCE group and 45 cases in the non-RCE group (9.0%(30/333) vs. 6.5%(45/689), χ²=2.027, P=0.155). The diagnostic time of AL was 9(5) days postoperative (range: 4 to 30 days). Among them, 23 cases showed cervical leakages, 50 cases showed intro-thoracic leakages, and 2 cases both cervical and intro-thoracic leakages. The diagnostic time of patients with intro-thoracic leakages was longer than that of cervical leakages (10(4) days vs. 6(3) days, Z=-2.517, P=0.012). Among the 333 patients in the RCE group, 16 cases of RCE indicated leakages including 11 cases of true positive and 5 cases determined to be false positive, while 317 cases indicated no abnormalities including 19 cases developed leakages. The sensitivity and specificity of RCE to detect AL were 36.7%(11/30) and 98.3%(298/333), respectively. The Youden-index was 0.35, and the diagnostic accuracy was 92.8%(309/333). The positive and negative predictive value were 11/16 and 94.0%(298/317), respectively. Conclusions: Routine contrast esophagram after three-incision esophagectomy with cervical anastomosis has low sensitivity and high specificity in the diagnosis of AL. The diagnostic time of AL is the 9th day after surgery. It is necessary to prolong the observation time clinically, and combine RCE with CT, endoscopy and other inspection methods for diagnosis.

[Lymphocyte activation gene 3 expression on T lymphocyte cell subsets in patients with myelodysplastic syndrome].

Objective: To investigate the expression of Lymphocyte activation gene 3 (LAG3) in myelodysplastic syndromes (MDS) patients. Methods: A total of 16 MDS patients newly diagnosed in Hematology Department of Tianjin Medical University were enrolled from January to November 2019. The healthy control (HC) group includes 16 cases of healthy adults. The expression levels of LAG3 on CD8(+)T cells, CD4(+)T cells and regulatory T cells (Treg) in MDS patients and healthy controls were detected by flow cytometry. Results: A total of 16 patients with MDS were included, including 5 males and 11 females, with a median age of 56 (18-80) years old. HC group includes 16 healthy adults, 8 men and 8 women, with a median age of 40 (17-69) years. There was no statistically significant difference in gender and age composition between the two groups (both P>0.05). The expression of LAG3 on CD8(+)T cells in MDS patients (74.45%±22.31%) was significantly higher than that in HC group (58.78%±14.82%, P<0.05). The LAG3 expression on Treg in MDS patients (64.91%±10.32%) were significantly higher than that of HC group (49.09%±13.58%, P<0.05). There was no statistical difference in LAG3 expression on CD4(+)T cells between the two groups. Conclusion: The expression of LAG3 on CD8(+)T cells and Treg increases in MDS patients than that of healthy people.

[The predictive value of ultrasonic measurement of the diaphragmatic thickening fraction combined with the maximal inspiratory pressure in mechanical ventilation patients].

Objective: To evaluate the value of the diaphragmatic thickening fraction (DTF) combined with the maximum inspiratory pressure (MIP) for the prediction of weaning success in mechanically ventilated patients. Methods: Patients admitted to the intensive care unit (ICU) of Yijishan Hospital of Wannan Medical College and on mechanical ventilation for 24 hours from June 2018 to April 2019 were selected as the study subjects. A low-level pressure support ventilation (PSV) method was applied to conduct a spontaneous breathing test (SBT) for 30 minutes after the patients met the screening conditions for clinical weaning; and the patients were weaned when they met the clinical weaning criteria. Before weaning, the patient's MIP was measured. The right hemidiaphragmatic excursion (DE) and the thickness of the diaphragm at the end of inspiration and at the end of exhalation were measured by ultrasound, and the DTF was calculated. The statistical relationship between the DTF, DE and MIP was analyzed. The predictive value for the success of weaning was calculated with the DTF, DE and MIP and was evaluated by the area under the receiver operating characteristic curve (AUC). Results: A total of 73 patients were included in this study, including 57 patients who were successfully weaned, and 16 patients who experienced failure. The DTF of the successful weaning group (35%, 8%) was significantly higher than that of the failed weaning group (25%±5%), and the difference was statistically significant (t=6.401, P<0.01). The MIP (34±9 cmH(2)O) in the successful weaning group was significantly higher than that in the failed weaning group (23±3 cmH(2)O), and the difference was statistically significant (t=7.186, P<0.01). The ROCs for the DTF, MIP, and diaphragmatic displacement were 0.907, 0.896, and 0.749, respectively. A DTF ≥ 27.78%, with a sensitivity of 92.98%, a specificity of 81.25%, and an AUC of 0.907 (95% CI: 0.816-0.963), was used as the standard to predict the success of weaning. An MIP>26.5 cmH(2)O, with a sensitivity of 80.7%, a specificity of 93.75%, and an AUC of 0.896 (95% CI: 0.803-0.955), was used as the standard to predict the success of weaning. The AUC of DTF ≥ 27.78% and MIP ≥ 26.5 cmH(2)O was 0.920 (95% CI:0.832-0.971), and the specificity increased to 87.7%, but the sensitivity was slightly reduced to 87.5%. Conclusions: The DTF and MIP play a crucial role in determining the appropriate time and predicting the outcome of weaning of mechanical ventilation patients. Compared with the DTF and MIP alone, the DTF combined with MIP greatly improved the accuracy of predicting successful weaning.

[Application of adaptie statistical iterative reconstruction technology combined with low tube voltage in three phase enhanced low dose liver scanning].

Objective: To explore the application value of adaptive statistical iterative reconstruction (ASIR) combined with low tube voltage in three-stage enhanced low-dose scan of liver. Methods: From March 2017 to November 2017, two groups which each group included 50 patients were randomly selected at the Second Affiliated Hospital of Harbin Medical University with different stages of arterial phase, delayed phase and portal vein scanning. GE Discovery CT 750 HD Liver CT Ⅲ was used during enhanced scanning. A total of 100 patients included 56 males and 44 females, aged 27-73 years old and 42 patients with hepatocellular carcinoma, 44 patients with hepatic hemangioma, and 14 patients with other diseases. The arterial and delayed period of group A patients were scanned with a low dose of 100 kV+ASIR, and the portal vein phase was conventional. Dosage scanning was 120 kV+FPP; the arterial and delayed period of group B was normal dose scanning, 120 kV+FPP, and the portal vein phase was low dose scanning, 100 kV+ASIR. At the same time, FBP reconstruction was used for all low-dose scanning phases to obtain low-dose images under normal reconstruction mode. The objective evaluation index of image quality was analyzed by completely randomized design analysis of variance, and Dunnett-t test was used to compare the two groups. For the subjective evaluation part, the rank sum test of multiple groups was used. Results: ASIR combined with low tube voltage enhanced low dose scanning in the third phase of the liver, and the radiation dose decreased by 37% in the low dose group compared with the normal dose group. There was no statistically significant difference between the low dose group (100 kV+ASIR) and the normal dose group (120 kV+FPP) in subjective image quality evaluation (P>0.05); objective evaluation of image quality except for low dose(100 kV+ASIR) portal stage noise slightly worse than conventional dose group (120 kV+FBP) (low dose 10.86±1.98, conventional dose 9.40±2.12, P<0.05), the other indexes in each period were superior or indifferent to the normal dose group. Conclusion: ASIR technique combined with low tube voltage can be used in the third phase of liver enhanced low-dose scanning and the image quality is improved.

Reliable sonographic features for nodal thyroglobulin to diagnose recurrent lymph node metastasis from papillary thyroid carcinoma.

OBJECTIVES: Ultrasound-guided aspiration cytology (US-FNAC) was previously used to diagnose lymph node metastasis of papillary thyroid carcinoma (PTC). Combined US-FNAC with nodal thyroglobulin (LN-FNA-Tg) significantly improved the diagnostic rate. However, diagnostic accuracy depends on proper node selection. Therefore, it is crucial to choose the nodes with reliable sonographic features to guide clinician for confirmation. DESIGN AND SETTING: Retrospective cohort study was carried out in one medical centre from 2011 to 2014. PARTICIPANTS: A total of 148 patients with PTC, being treated by total thyroidectomy and radioiodine, were assessed for potential nodal metastases by ultrasound. MAIN OUTCOME MEASURES: Lymph nodes with cystic content, peripheral hypervascularity, calcification, hyperechoic content, the absence of hilum and Solbiati index < 2 indicated risk of malignancy. US-FNAC and LN-FNA-Tg were both performed. Positive nodal metastasis was further confirmed by dissection. Risk impact of these sonographic features on LN-FNA-Tg to diagnose nodal metastasis was tested by logistic regression analysis based on the significance in both univariate and multivariate models. RESULTS: Overall, 49 lymph nodes were documented as recurrent nodal metastasis. LN-FNA-Tg greater than serum thyroglobulin and higher than 1 ng/mL achieved 100% of diagnostic rate for recurrent nodal metastasis. The malignant sonographic features that significantly cohered with positive LN-FNA-Tg were cystic and hyperechoic content and lack hilum, in sequence. CONCLUSIONS: LN-FNA-Tg is an excellent tool to quantitatively diagnose nodal metastasis. To achieve ideal diagnosis, the most reliable sonographic features were cystic content, hyperechoic content and the absence of hilum in lymph nodes, but not calcification or Solbiati index < 2.

[Study on the transfer mechanism and destructive law of the bacterial antibiotic resistance genes disinfected by chlorination].

Objective: To study the response of Escherichia coli (E. coli) HB101 (plasmid pUC19) and its carried antibiotic resistance genes to the process of cholorination under different environmental conditions. Methods: The E. coli strain was reacted with sodium hypochlorite at the concentration of 0.5, 0.75, 1.00, and 0.55 mg/L, then the residual chlorine and the colonies were detected at the 0.25, 1, 2, 5, 10, 20, and 30 min of the reaction, respectively. The first order disinfection kinetic model and EFH model were used to evaluate the inactivation effect of E. coli (plasmid pUC19) treated by sodium hypochlorite, while the plasmid pUC19 and antibiotic resistance gene amp(r) were detected by PCR method. Besides, the logarithm of Ct (residual chlorine in t) under different concentration were calculated. Results: The temperature and pH value played important roles on the inactivation of E. coli and elimination of plasmid pUC19 and amp(r) under the function of sodium hypochlorite. The Ct value needed for 5-log of E.coli HB101(pUC19) inactivation at 4, 20, 36 ℃ was 11.92, 10.28, 7.67, respectively, and when the pH was in 6.0, 7.0, 8.0, with chloride concentration were 0.75, 0.70, 0.55 mg/L, the Ct value needed for reached to 6.68, 10.28, 15.73 min·mg/L. At pH 7.2 condition, when the temperature was 4, 20, 36 ℃, and chloride concentration were 9, 5, 3 mg/L.The required Ct values to completely destroy the transformation function of free antibiotic resistant plasmids were 36.11, 34.17,16.09 min·mg/L. Sodium hypochlorite disinfection can release free ampr gene and even the transformed plasmid pUC19, and pollute the water body. Only when the Ct value reached 903.03 min·mg/L, the complete ampr gene can be destroyed which was far more exceed the bacterial lethal Ct value. Conclusion: Even if all the antibiotic resistant bacteria were inactivated, the antibiotic resistant plasmids or genes might still maintain complete with the transformable function, which may result in new potential risks of waterborne diseases.

[Comparison of the effect of lymph node dissection performed by Ivor-Lewis or left-sided thoracic esophagogastrectomy for Siewert type â ¡ adenocarcinoma of the esophagogastric junction].

Objective: To compare the extent of lymphadenectomy and postoperative complications between Ivor-Lewis procedure and left sided thoracotomy in patients with Siewert type Ⅱ adenocarcinoma of the esophagogastric junction (AEG). Methods: The clinical data of 101 patients with Siewert type Ⅱ EG who received surgical treatment between January 2014 and September 2015 in the Department of Esophageal Cancer, Tianjin Medical University Cancer Hospital were analyzed retrospectively. These patients were divided into Ivor-Lewis group (IL, n=38) and left- sided thoracotomy group (LT, n=63) according to the operation mode. The number and extent of dissected lymph nodes and postoperative complications were compared between the two groups. Results: The surgical blood loss, length of postoperative stay, anastomotic leakage, pulmonary infection, respiratory failure and complications of incision of the two groups showed no significant differences (P>0.05 of all). The operation time of IL group was 200 min, significantly longer than the LT group (120 min, P<0.05). The number of resected lymph nodes in the IL and LT groups were (20±9) and (13±7), respectively, with a statistically significant difference (P<0.001). Significantly more thoracic lymph nodes (7±5) were harvested in the IL group than in the LT group (2±2, P<0.001), and the number of resected abdominal lymph nodes in the IL and LT groups were (13±8) and (11±7), with a non-significant difference (P=0.157). As regarding the lymph node dissection rate, the IL approach was obviously better than the LT approach in the following lymph node stations: superior mediastinal nodes, subcarinal nodes, left hilar nodes, right hilar nodes, middle thoracic paraesophageal nodes, lower thoracic paraesophageal nodes, lymph nodes along the common hepatic artery, and lymph nodes along the splenic artery(P<0.05 for all). Conclusions: The Ivor-Lewis procedure achieves better thoracic and abdominal lymph node dissection, and does not cause more postoperative complications than the left-sided thoracotomy in patients with Siewert type Ⅱ AEG. However, these findings need to be confirmed by large-scale randomized clinical trial in the future.

[Value of multi-slice spiral CT in preoperative diagnosis of pancreatic cancer].

Objective: To analyze the diagnostic value of multi-slice spiral computed tomography (MSCT) in preoperative tumor staging, lymphatic metastasis, vascular invasion and perineural invasion. Methods: From January 2013 to December 2015, MSCT images of 87 patients from the Second Hospital of Harbin Medical University who were examined by contrast-enhanced MSCT and diagnosed as pancreatic cancer by surgical pathology within 2 weeks were collected.MSCT images were retrospectively analyzed to evaluate the tumor staging, lymphatic metastasis, vascular invasion and perineural invasion and then compared with surgical pathology.Kappa test and receiver operation characteristic (ROC) curve were used to evaluate the diagnostic value of MSCT in pancreatic cancer. Results: The overall accuracy of MSCT in T staging of pancreatic cancer was 85.1% (kappa =0.67, P<0.01); the accuracy of T1, T2, T3 and T4 staging were 75.0%, 57.1%, 95.0% and 66.7%; the sensitivity were 75.0%, 80.0%, 87.7% and 75.0%; the specificity were 98.8%, 92.2%, 86.4% and 96.2%; the positive predictive value (PPV) were 75.0%, 57.1%, 95.0% and 66.7%; the negative predictive value (NPV) were 98.8%, 97.3%, 70.4% and 97.4%.The accuracy, sensitivity, specificity, PPV and NPV of MSCT in diagnosing lymphatic metastasis were 62.1%, 62.3%, 61.5%, 79.2% and 41.0%.The accuracy, sensitivity, specificity, PPV and NPV of MSCT in diagnosing vascular invasion were 94.3%, 78.6%, 97.3%, 84.6% and 95.9%.The accuracy, sensitivity, specificity, PPV and NPV of MSCT in diagnosing MSCT perineural invasion were 80.5%, 81.1%, 76.9%, 95.2% and 41.7%.The area under curve (AUC) was 0.79(95%CI 0.68-0.90, P=0.001). Conclusion: Contrast-enhanced MSCT plays important roles in evaluation of preoperative tumor staging, vascular invasion and perineural invasion of pancreatic cancer while it has little value on diagnosis of lymphatic metastasis.

[NIX-mediated mitochondrial autophagy in pathogenesis of myelodysplastic syndrome anemia].

Objective: To investigate the change of NIX level of bone marrow nucleated red blood cells in anemia patients with myelodysplastic syndromes (MDS), to explore the significance of NIX-mediated mitochondrial autophagy in the pathogenesis of MDS anemia. Methods: A total of 54 patients with MDS diagnosed in the Department of Hematology of General Hospital, Tianjin Medical University from July 2015 to July 2016 were enrolled into the MDS group, 33 cases of immune thrombocytopenia or idiopathic leukopenia as controls.The level of NIX, the number of mitochondria, mitochondrial membrane potential, the level of reactive oxygen species (ROS) in GlycoA(+) nucleated red blood cells were measured by flow cytometry; the level of NIX mRNA was measured by PCR. Results: (1) The expression of NIX in GlycoA(+) nucleated red blood cells in high-risk MDS patients (0.61±0.24) was significantly lower than that in controls (0.79±0.16, P=0.027), and lower than that in low-risk MDS patients (0.81±0.15, P=0.011), while there was no significant difference between the controls and low-risk MDS patients. The expression of NIX mRNA in GlycoA(+) nucleated red blood cells in high-risk MDS group (0.36±0.09) was lower than that in the controls (1.44±0.41, P=0.027) and that in the low-risk group (1.02±0.22, P=0.012); there was no significant difference between the controls and the low-risk group. (2) The number of mitochondria in GlycoA(+) nucleated red blood cells in high-risk MDS patients (937.17±707.85) was significantly higher than that in the controls (513.49±372.33, P=0.019) and that in low-risk MDS patients (461.74±438.02, P=0.008); while there was no significant difference between low-risk MDS patients and the controls. (3) The level of mitochondrial membrane potential in GlycoA(+) nucleated red blood cells in high-risk MDS patients (0.33±0.18) was significantly lower than that in the controls (0.61±0.32, P=0.001) and that in low-risk MDS patients (0.61±0.34, P=0.001); with no significant difference between low-risk MDS patients and the controls. (4)The level of ROS in GlycoA(+) nucleated red blood cells in high-risk MDS patients (438.65±322.83) was significantly higher than that in the controls (242.77±136.87, P=0.006), and higher than that in low-risk MDS patients (197.40±95.07, P=0.001); no significantly different between low-risk MDS patients and the controls. (5) The number of mitochondria in GlycoA(+) nucleated red blood cell was positively correlated with the percentage of ring sideroblast (r=0.457, P=0.028) in the MDS patients.(6) The number of mitochondria in GlycoA(+) nucleated red blood cells was negatively correlated with the concentration of hemoglobin (r=-0.521, P=0.009) in high-risk MDS patients, but not correlated with the concentration of hemoglobin in low-risk MDS patients. Conclusion: NIX level is reduced in nucleated red blood cells of high-risk MDS patients, which leads to impaired mitochondrial autophagy, increased damaged mitochondria and apoptosis of nucleated red blood cells, thus related with anemia.

[Comparison of the prognostic value of the seventh and eighth edition of The AJCC Esophageal Cancer Staging System for the patients with stage â ¡ and â ¢esophageal squamous cell carcinoma].

Objective: To compare and evaluate the prognostic value of the 7(th) and 8(th) edition of The AJCC Esophageal Cancer Staging System for patients with stage Ⅱ and Ⅲ esophageal squamous cell carcinoma. Methods: The clinical data of 328 esophageal cancer patients who received operation at Department of Esophageal Cancer, Tianjin Tumour Hospital from January 2006 to December 2010 were restrospectively analyzed. There were 63 female and 265 male patients. The mean age was 65 (range: 33 to 87) years. Univariate and multivariate analysis were performed to identify the prognosis factors. Results: The five years overall survival rates among patients with stage Ⅱ and Ⅲ were both significantly different (χ(2)=87.035, 84.730, all P=0.000) according to the 7(th) and 8(th) editions of the TNM staging systems. The five years overall survival rate among patients with stage ⅡB and ⅢA were significantly different (39.6% vs 23.4%, P=0.001) according to the 7(th) edition of the esophageal cancer staging systems.According to the 8(th) edition of the esophageal cancer staging system, the 5 years survival rate of patients with stage ⅡA and ⅡB, ⅢB and Ⅳ was statistically significant (58.5% vs. 35.5%, P=0.040; 18.9% vs. 0, P=0.000). In multivariate analysis, tumor size, T staging, N staging and tumor differentiation (HR=1.592, 95%CI: 1.185 to 2.139, P=0.002; HR=1.519, 95% CI: 1.236 to 1.867, P=0.000; HR=1.647, 95% CI: 1.448 to 1.874, P=0.000; HR=1.404, 95% CI: 1.059 to 1.861, P=0.018) were the main independent prognosis factors affecting the prognosis of esophageal squamous cell carcinoma patients. Conclusions: Both the 7(th) and the 8(th) editions of TNM staging systems are able to reflect the clinical prognosis of patients receiving radical resection of esophageal cancer, and the factors of tumor size, differentiaton, invasion depth and lymph node metastases are the independent predictors of prognosis. The 8(th) edition provides a more detailed and more reasonable for the staging of stage Ⅱ and Ⅲ for esophageal cancer patients than the 7(th) edition, and it is more accurate for the prognosis of patients with esophageal cancer after surgery.

[Lymph node metastasis and prognostic factors for T1 esophageal cancer].

Objective: To evaluate the lymph node metastasis (LNM) pattern and related prognostic factors for T1 esophageal cancer. Methods: Clinical data of 143 cases of pT1 esophageal cancer patients (120 male and 23 female patients with median age of 60 years) who underwent esophagectomy and lymph node resection during January 2011 and July 2016 at the Department of Esophageal Cancer of Tianjin Medical University Cancer Institute and Hospital were reviewed, including 50 cases of T1a patients and 93 cases of T1b patients. The LNM pattern was analyzed and the prognostic factors related to LNM were assessed by χ2 test and Logistic regression analysis. Results: Of 143 patients, 25 patients had LNM. The LNM rates were 17.5% for pT1 tumors, 16.0%(8/50) for pT1a tumors, and 22.6%(21/93) for T1b tumors. Of 25 patients with LNM, one patient had cervical metastasis, 15 patients with thoracic metastasis, and 17 patients with abdominal metastasis. The relatively highest LNM sites were laryngeal recurrent nerve (8 cases), left gastric artery (8 cases), right and left cardiac (6 cases) and thoracic paraesophageal (5 cases). Logistic regression analysis showed that the depth of tumor infiltration (OR=4.641, 95%CI: 1.279 to 16.836, P=0.020), tumor size (OR=5.301, 95%CI: 1.779 to 15.792, P=0.003), tumor location (OR=3.238, 95% CI: 1.248 to 8.401, P=0.016), and tumor differentiation (OR=5.301, 95%CI: 1.719 to 16.347, P=0.004) were independent prognostic factors related to LNM for T1 esophageal cancer. Tumor size (OR=4.117, 95% CI: 1.228 to 13.806, P=0.022) was an independent risk factor related to thoracic LNM, and the vessel invasion (OR=6.058, 95% CI: 1.228 to 29.876, P=0.027) and tumor location (OR=8.113, 95% CI: 1.785-36.872, P=0.007) were independent prognostic factors related to abdominal LNM. Conclusions: T1 esophageal cancer has a relatively high LNM rate, and the depth of tumor infiltration, tumor size, tumor location and tumor differentiation are correlated with LNM. The LNM risk and extent must be considered comprehensively in decision-making of a better surgical treatment and lymph node resection strategy.

[An investigation for standardized diagnosis and treatment of idiopathic normal-pressure hydrocephalus].

OBJECTIVE: To investigate some important issues for diagnosis and treatment of idiopathic normal-pressure hydrocephalus (iNPH), such as standardized pre-operative assessment, initial pressure value of diverter pump, and pressure regulation during follow-up. METHODS: Twenty six iNPH patients (21 males) who treated in Department of Neurosurgery of 2nd Affiliated Hospital of Zhejiang University School of Medicine from 2011 to 2015 were analyzed retrospectively. The average age was 60.5 year. The analysis focused on the treatment process of iNPH, initial pressure value of diverter pump, choice of diverter pump, and pressure regulation during follow-up. RESULTS: As a result, 24 cases (92.3%) had a good prognosis based on their imaging and clinical manifestations. Based on the literature and their clinical experiences, this department established a diagnosis and treatment procedure of iNPH and a pressure regulation procedure for the follow-up of iNPH. Moreover, it is proposed that choosing an anti-gravity diverter pump and making an initial pressure value 20 mmH2O less than pre-surgical cerebrospinal pressure may be beneficial for the prognosis. CONCLUSION: This standardized diagnosis and treatment procedure for iNPH is practical and effective.

Experimental study on angiogenesis in a rabbit VX2 early liver tumour by perfusion computed tomography.

Ten rabbits implanted with VX2 liver tumours were investigated by perfusion computed tomography (PCT) imaging 1 week (early) and 2 weeks (late) after tumour induction; 10 other rabbits were non-implanted controls. Time-density curves, perfusion parametric maps and perfusion parameters were obtained for tumour rim and normal tissue surrounding the tumour, and for liver tissue from the controls. In addition, microvessel density (MVD) and vascular endothelial growth factor (VEGF) were studied by immunohistochemistry 2 weeks after tumour implantation. A deconvolution mathematical model was used to calculate hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), capillary vessel surface permeability (PS) and hepatic arterial index (HAI). At the tumour rim on the early PCT scan, MTT was significantly lower whereas HBF, HBV, HAI and PS were significantly higher than in surrounding normal tissue. There were no significant changes in perfusion parameters on the late PCT scan compared with the early scan. Significant linear correlations of MVD and VEGF were found with HBF, PS and HAI, but not with HBV or MTT. It is concluded that PCT imaging is useful for the evaluation of tumour angiogenesis and for the early detection of liver tumours.

[Study on autophagy in nucleated red blood cells in patients with myelodysplastic syndromes].

Objective: To investigate the change of autophagy level of bone marrow nucleated red blood cell (RBC) in patients with myelodysplastic syndromes (MDS) . Methods: Fifty-four MDS patients and thirty-three controls were enrolled in this study. The mitophagy were observed by transmission electron microscopy (TEM) . The level of autophagy-associated protein LC3B in GlycoA(+) nucleated RBC was measured by flow cytometry. The expressions of ULK1 and mTOR mRNA in GlycoA(+) nucleated RBC were measured by real-time PCR. The expression of the mitochondrial outer membrane protein TOM20 in GlycoA(+) nucleated RBC was detected by Western blot. Results: Autophagosomes or autolysosomes were scarcely observed by TEM in MDS patients. The expression of LC3B in GlycoA(+) nucleated RBC in high-risk MDS patients (0.22±0.12) was significantly lower than that in normal controls (0.43±0.22, P<0.001) , and lower than that in low-risk MDS patients (0.40±0.16, P=0.001) . The expression of AMPK [0.26 (0.60) ] in GlycoA(+) nucleated RBC in high-risk MDS patients was significantly lower than that in controls [1.00 (2.07) , P<0.017) . The expression of ULK1 mRNA in GlycoA(+) nucleated RBC in high-risk MDS patients [0.27 (3.31) ] was significantly lower than that in controls [1.07 (4.41) , P<0.017]. The level of mTOR mRNA in GlycoA(+) nucleated RBC in high-risk MDS patients [1.82 (3.74) ] was significantly higher than that in controls [1.26 (1.38) , P<0.017]. The level of LC3B in GlycoA(+) nucleated RBC was negatively correlated with the HGB (r=0.529, P=0.009) in high-risk MDS patients. The expression of mitochondrial outer membrane protein TOM20 in high-risk MDS patients was 9.42±4.42. Conclusion: Autophagy is impaired in nucleated RBC of MDS patients.

[Characteristic and function of peripheral blood mononuclear cells-induced macrophages in patients with myelodysplastic syndrome].

Objective: To explore characteristic and function of peripheral blood mononuclear cells (PBMNC) -induced macrophages in patients with myelodysplastic syndrome (MDS) to couple with its progression. Methods: A total of 24 MDS patients (11 low-risk patients and 13 high-risk group patients) referred to Department of Hematology of Tianjin Medical University General Hospital and normal controls were enrolled from September 2014 to December 2015. PBMNC was stimulated with GM-CSF to transform to macrophages. The morphology of macrophages was observed by microscope. The quantity of macrophages, CD206 and SIRPα on surface of macrophages were detected by flow cytometry. The phagocytic function of macrophages was analyzed by fluorescence microscopy and flow cytometry. Results: The morphology of macrophages from MDS patients was abnormal. The percentage of transformed macrophages was (5.17±3.47) % in patients with MDS, which was lower than that in controls significantly[ (66.18±13.43) %, t=3.529, P=0.001]. The expression of CD206 on macrophages from MDS patients was significantly lower than that of controls[ (9.73±2.59) % vs (51.15±10.82) %, t=4.551, P<0.001]. The SIRPα level of macrophages from MDS patients was significantly lower than that of controls [ (0.51±0.09) % vs (0.77±0.06) %, t=2.102, P=0.043]. The phagocytic index and the percentage of phagocytic of macrophages from MDS patients were significantly lower than those of macrophages from normal controls[0.45±0.08 vs 0.92±0.07, t=-6.253, P=0.008; (23.69±3.22) % vs (42.75±2.13) %, t=-6.982, P=0.006 respectively]by flow cytometry. The phagocytic index of MDS patients was significantly lower than that of controls (0.24±0.04 vs 0.48±0.96, t=3.464, P=0.001) by fluorescence microscopy. Conclusion: The quantity, recognization receptors and phagocytosis of PBMNC-induced macrophages decreased in MDS patients.

Functional magnetic resonance imaging and transcranial magnetic stimulation: complementary approaches in the evaluation of cortical motor function.

Functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) represent different approaches to mapping the motor cortex. fMRI identifies areas of hemodynamic changes during task performance while TMS provides electrophysiologic data concerning the localization and density of cortical motoneurons. Here we define the spatial correlation between fMRI and TMS maps and compared them with direct electrical cortical stimulation (ECS). We performed fMRI at 1.5 T on 3 normal subjects and 2 patients with mass lesions near the central sulcus using a multislice, asymmetric, spin-echo, echo-planar pulse sequence during the performance of a motor task. We also performed focal TMS with surface EMG recordings from the muscles primarily involved in the fMRI task. We coregistered the stimulation sites in real time with the fMRI maps using a frameless stereotactic system. In both patients we also performed ECS of the cortex during surgery under local anesthesia. fMRI maps were validated by the electrophysiologic data both pre- and intraoperatively. Our results suggest that regions of fMRI activation correspond spatially to areas of highest motoneuron density as demonstrated by electrophysiologic techniques.

Synthesis and antimalarial activity of artemisinin derivatives containing an amino group.

In search of water-soluble artemisinin derivatives that are more stable than sodium artesunate, over 30 derivatives containing an amino group (compounds 3-5) were synthesized and tested in mice. All products tested (except 5a and 5b) are the beta isomers. These basic compounds combined with organic acids (oxalic acid, maleic acid, etc. ) to yield the corresponding salts. Generally, the maleates have better solubility in water than the corresponding oxalates. The aqueous solutions of these salts can be kept at room temperature for several weeks without any discernible decomposition. Compounds 3f, 3h, and 3r are much more active against P. berghei than artesunic acid by oral administration and therefore were further tested in monkeys. However, their oral efficacies are poorer than that of artesunic acid against P. knowlesi in rhesus monkeys. It is interesting to note that 3f, 3h, and 3r showed much lower efficacies against P. berghei when they were administered subcutaneously than orally.