[Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy].

Objectives: To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model. Methods: This was a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method,patients were randomly divided into a model group(n=166) and a validation group(n=41) according to an 4︰1 ratio. There were 118 males and 48 females in the modeling group,with an age (M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (rang: 25.0~81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the risk of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,followed by internal and external validation of the model. Results: Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT,D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set,and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model(P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806,suggesting that the model had a good generalization prediction ability. Conclusions: The levels of ALT,D-dimer,and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

[Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase â ¡ trial].

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

[Comparison of follow-up treatment regimens for colorectal cancer liver metastases without objective response to neoadjuvant chemotherapy: direct surgery or surgery after second-line chemotherapy].

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

[Pay attention to standardized treatment of hepatocellular carcinoma].

Hepatocellular carcinoma is a serious disease that threatens the health of Chinese people. At present,various treatments for hepatocellular carcinoma have their own advantages and disadvantages,which are suitable for its specific individual patient. This article makes a brief review about the importance of standardized treatment for hepatocellular carcinoma. Meanwhile,it should be noticed that standardized staging system is the prerequisite for making a reasonable treatment plan,standardized pathological diagnosis is the basis of comprehensive treatment,standardized treatment is the key to the efficacy,and the multidisciplinary team is the organizational basis for standardized treatment.

[A comparative study of total laparoscopic and laparoscopic-assisted simultaneous resection for colorectal cancer liver metastasis].

Objective: To compare the safety and outcome between total laparoscopic and laparoscopy-assisted synchronous resection for colorectal cancer patients with liver metastases. Methods: The data of patients who underwent total laparoscopic or laparoscopy-assisted simultaneous resection of primary colorectal cancer and liver metastases in our hospital between December 2008 and December 2016 were collected and analyzed. The total laparoscopic surgery patients were matched 1∶2 to the laparoscopy-assisted surgery patients based on the propensity score. 22 patients were classified in the total laparoscopic group and 44 patients were classified in the laparoscopy-assisted group. The intraoperative conditions and postoperative outcomes of the two groups were compared. Results: There was no difference in the preoperative baseline data between the two groups (P>0.05). The median operative time were 317.50 and 267.50 minutes in the total laparoscopic group and the laparoscopy-assisted group, respectively, and the median intraoperative blood loss were 100 and 200 ml, both with no statistically significant differences (P>0.05). There were 1 case of intraoperative blood transfusion in the total laparoscopic group and 5 cases in the laparoscopy-assisted group, with no statistically significant difference (P=0.650). The median postoperative hospital stay in the two groups were 11.0 and 10.0 days, the median postoperative defecation time were 4.0 and 4.0 days and postoperative complication rates were 13.6% and 20.5%, and none of these differences were statistically significant (P>0.05). However, no Clavien-DindoⅡ level and above complications occurred in total laparoscopic group. The median disease-free survival (DFS) were 15.0 and 15.7 months in the total laparoscopic group and the laparoscopy-assisted group, the overall survival (OS) were 25.9 and 37.6 months, respectively, with no statistically significant differences (P>0.05). Conclusion: Laparoscopy-assisted approaches are similar, so the appropriate approach should be chosen according to the clinical condition and surgeon's experience.

[Clinical characteristics and efficacy analysis of secondary benign paroxysm positional vertigo after middle ear surgery].

Objective:To investigate the clinical characteristics and therapeutic effect of benign paroxysm positional vertigo（BPPV） secondary to middle ear surgery. Method:A total of 1 126 patients who underwent tympanoplasty or radical mastoidectomy due to chronic suppurative otitis media and middle ear cholesteatoma in our hospital from January 2014 to December 2018 were collected. Clinical data of BPPV within 1 month after surgery were collected, The incidence, incidence side, involved semicircular canal, onset time, age of onset, and duration of operation of secondary BPPV after middle ear surgery were analyzed. All patients with secondary BPPV were treated by manual reduction, and the efficacy was evaluated 1 day, 1 week, and 1 month after reduction. Result:2.13% （24 cases） of patients had secondary BPPV after operation, among which 2 cases were parietal incidence. 18 cases were involved in posterior semicircular canals and 6 cases were horizontal semicircular canals. The onset time was 1-12 days after the operation, with an average of （3.29±2.44） days. The mean age of onset was （51.62±10.15） years old, and there was no statistically significant difference between the age of patients without BPPV after middle ear surgery （P>0.05）. The average operating time was （97.29±14.78） minutes, showing no statistically significant difference compared with patients in the group without BPPV （P>0.05）. Fourteen cases （58.3%） were cured and 10 cases were improved after 1 day evaluation. Evaluated 1 week after treatment, 19 cases （79.17%） were cured and 5 cases were improved. Evaluated 1 month after treatment, all patients were cured without recurrence. Conclusion:BPPV secondary to middle ear surgery often appears 3 days after surgery, and the posterior semicircular canal of the operative ear is most commonly involved. Age and operation duration have no significant influence on the incidence of BPPV, and satisfactory therapeutic effect can be obtained through manipulative reduction.

[Trend analysis of age of diagnosis for liver cancer in cancer registry areas of China, 2000-2014].

Objective: To investigate trends of mean age of diagnosis for liver cancer during 2000 to 2014, which may provide basic information for making feasible cancer prevention strategies. Methods: Based on the continuous cancer incidence data from 22 cancer registries of China between 1 January 2000 and 31 December 2014, the incidence by birth-cohort (year of birth between 1925 and 1994) and age specific incidence rates were calculated. The incidence of different age groups were also calculated. World Segi's population was used for age standardization. The liner regression model was applied to analyze the changing trend of mean age of diagnosis. Results: In 2014, the incidence rate for population with 80 years older and above was 108.21 per 100 000, whereas the rate for population at 30-39 years old was 5.09 per 100 000. But the mean age of diagnosis for liver cancer showed an increasing trend from 2000 to 2014. For male, it had increased from 58.80 to 62.35 (t=18.70, P<0.001) . For female, it had increased from 64.02 to 68.99 (t=20.50, P<0.001) . After age standardization, the mean age of diagnosis still showed increasing trend. Meanwhile, the proportion of liver cancer in people above 70 years old was 25.05% in 2014, which was higher than that in 2000 (22.49%). Conclusion: The mean age of liver cancer incidence was increasing during 2000-2014.

[Correlation between postoperative neutrophil to lymphocyte ratio and recurrence and prognosis of hepatocellular carcinoma after radical liver resection].

Objective: To investigate the correlation between postoperative peripheral blood neutrophil to lymphocyte ratio (NLR) and recurrence and prognosis of patients with hepatocellular carcinoma (HCC). Methods: The clinicopathological and follow-up data of 344 patients with HCC who underwent radical liver resection from May 2010 to April 2014 were analyzed retrospectively. Results: Of the 344 patients, 104 had early recurrence and 84 had late recurrence. Receiver operating characteristic (ROC) curve analysis showed that the NLR predicted area under the curve (AUC) of early recurrence was 0.622 (P<0.001), the optimal cut-off value was 2.41. The AUC of late recurrence was 0.634 (P=0.001), the optimal cut-off value was 2.15. Cox multivariate analysis showed the serum concentration of hepatitis B surface antigen (HR=2.508, 95% CI: 1.311-4.798), microvascular invasion (HR=2.422, 95% CI: 1.239-4.734), Milan criteria (HR=2.373, 95% CI: 1.427-3.948) and postoperative NLR (HR=2.285, 95% CI: 1.379-3.788) were independent risk factors of early recurrence after HCC resection. Postoperative NLR (HR=2.927, 95% CI: 1.630-5.255), liver cirrhosis (HR=2.531, 95% CI: 1.291-4.962) and serum concentration of albumin (HR=2.257, 95% CI: 1.251-4.073) were independent risk factors of late recurrence after HCC resection. The median recurrence-free survival (RFS) of the 344 patients was 45.0 months, and the median overall survival (OS) was 63.2 months. ROC curve analysis showed that the postoperative NLR predicted 5-year survival AUC was 0.689 (P<0.05), with an optimal cutoff of 2.29. Cox multivariate analysis showed microvascular invasion (HR=2.247, 95% CI: 1.534-3.291), postoperative NLR (HR=2.217, 95% CI: 1.653-2.974), and liver cirrhosis (HR=1.685, 95% CI: 1.168-2.431), Milan criteria (HR=1.679, 95% CI: 1.238-2.277), serum concentration of hepatitis B surface antigen (HR=1.623, 95% CI: 1.102-2.392), serum concentration of albumin (HR=1.43, 95% CI: 1.066-1.918) were independent factors of RFS after HCC resection, while microvascular invasion (HR=3.862, 95% CI: 2.407-6.197), Barcelona staging (HR=2.864, 95% CI: 1.600-5.125), postoperative NLR (HR=2.688, 95% CI: 1.782-4.055), liver cirrhosis (HR=2.039, 95% CI: 1.184-3.514), serum concentration of albumin (HR=1.81, 95% CI: 1.204-2.720) were independent factors of OS. Conclusions: For HCC patients who receive radical liver resection, postoperative NLR ≥2.29 implicates poor prognosis. Moreover, postoperative NLR ≥2.41 suggests early recurrence, while NLR ≥2.15 suggests late recurrence.

[A new prognostic score system of hepatocellular carcinoma following hepatectomy].

Objective: To establish a new scoring system based on the clinicopathological features of hepatocellular carcinoma (HCC) to predict prognosis of patients who received hepatectomy. Methods: A total of 845 HCC patients who underwent hepatectomy from 1999 to 2010 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. 21 common clinical factors were selected in this analysis. Among these factors, the cut-off values of alpha-fetoprotein (AFP), alkaline phosphatase (ALP) and intraoperative blood loss were evaluated by using a receiver operating characteristic (ROC) curve analysis.The Kaplan-Meier method and Cox regression model were used to evaluate the independent risk factors associated with the prognosis of HCC patients after hepatectomy. HCC postoperatively prognostic scoring system was established according to the minimum weighted method of these independent risk factors, and divided the patients into 3 risk groups, including low-risk, intermediate-risk and high-risk group. The relapse-free survival (RFS) and overall survival (OS) were compared among these groups. Results: The univariate analysis showed that clinical symptoms, preoperative α-fetoprotein (AFP) level, serum alkaline phosphatase (ALP) level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with median RFS of these HCC patients (P<0.05). Alternatively, clinical symptoms, preoperative AFP level, serum ALP level, tumor size, tumor number, abdominal lymph node metastasis, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, the severity of hepatic cirrhosis, intraoperative blood loss, the liver operative method, pathological lymphocyte invasion, pathological tumor thrombus, intraoperative blood transfusion, perioperative blood transfusion were significantly associated with the median OS of these HCC patients (P<0.05). The multivariate analysis showed that AFP ≥20 ng/ml, clinical symptoms, tumor diameter ≥5 cm, multiple tumors, macrovascular invasion or tumor thrombus, extrahepatic invasion or serosa perforation, moderate and severe liver cirrhosis, non- anatomic resection were the independent risk factors of RFS and OS (P<0.05). The independent risk factor of RFS was intraoperative bleeding loss ≥325 ml (P<0.05); The independent risk factors of OS were abdominal lymph node metastasis and pathological tumors thrombus (P<0.05). The respective weight of 11 independent factors was used to establish the scoring system (scores range from 0 to 26). In the score system, 0 to 5 points were defined as the low-risk group (286 cases), 6 to 12 points were determined as the intermediate-risk group (503 cases), more than 13 points were classified as the high-risk group (56 cases). The median RFS of the low-risk, intermediate-risk and high-risk group were 80, 27 and 6 months, respectively. The differences were statistically significant (P<0.001). The median OS of the three groups were 134, 51 and 15 months, respectively, and the differences were statistically significant (P<0.001). Conclusion: This new score system provides effective prediction of postoperative prognosis for HCC patients.

[Effect of different anesthetic techniques on the prognosis of hepatocellular carcinoma after hepatectomy].

Objective: To investigate the influence of different anesthetic techniques on the prognosis of hepatocellular carcinoma (HCC)after hepatectomy. Methods: A total of 185 consecutive patients with HCC confirmed underwent surgery in Cancer Hospital, Chinese Academy of Medical Sciences were recruited from January 2006 to January 2008. The patients were assessed as American Society of Anesthesiologists (ASA)Ⅰ-Ⅲ, with body mass index (BMI) (22.8±4.6)kg/m(2). There were 169 males, with an average age of 56 years old and 16 females, with an average age of 53 years old. According to the different anesthesia methods, 185 patients were divided into two groups: total intravenous anesthesia group (TIVA) (n=53) and intravenous-inhalation combined anesthesia group (n=132). Postoperative pain and adverse reactions were compared in recent follow-up, prognosis were compared in long-term follow-up. Results: Recent follow-up showed that the NRS scores 2 hours after operation in TIVA group was 2.0 (0-2.0), whereas those in intravenous-inhalation combined anesthesia group was 3.0 (1.0-3.0). The pain in TIVA groups was significantly lower than that in intravenous-inhalation combined anesthesia group (Z=-3.261, P=0.001). But for 24 hours after operation, the NRS scores in these two groups were 3.0 (2.0-5.0) and 3.0 (3.0-4.0), respectively. There was no significant difference in the two groups (Z=-0.035, P=0.972). In addition, there was no significant difference between the two groups in the incidence of sedation, nausea/vomiting, restlessness and other adverse reactions (all P>0.05). Long-term follow-up indicated that anesthetic techniques have no correlation with HCC prognosis in Kaplan-Meier analysis and Cox's regression analysis. Conclusion: There is no significant effect of two anesthesia methods on the long-term prognosis of HCC.

[Prognostic analysis of colorectal liver metastases treated by surgery combined with intraoperative radiofrequency ablation].

Objective: To investigate the clinical value of intraoperative radiofrequency ablation (RFA) in the treatment of colorectal liver metastasis (CLM). Methods: A retrospectively analysis of 187 patients with CLM who underwent liver resection with or without RFA from January 2009 to August 2016 in Department of Hepatobiliary Surgery, Cancer Hospital, Chinese Academy of Medical Sciences was performed. According to whether RFA was used intraoperatively, patients were divided into resection only group and combined treatment group. The clinical and pathological characteristics of the two groups were compared to explore factors influencing survival and recurrence. Imbalance of background characteristics between the two groups was further overcome by propensity score matching method (PSM). Results: The number of liver metastases (267), simultaneous liver metastases (100%), bilobar involvement (73.3%) and preoperative chemotherapy (93.3%) rates were significantly higher in the combined treatment group than those in the resection only group(471, 74.7%, 42.0% and 63.1%)(all P<0.05). In the combined treatment group, median overall survival (OS) was 25.7 months; and 3-year and 5-year OS were 47.9% and 28.8%, respectively. In the resection only group, the median survival time was 46.9 months; and 3-year and 5-year OS rate was 59.1% and 42.4%, respectively (χ(2)=4.579, P=0.034). Median disease-free survival (DFS) was 5.4 months in the combined treatment group, and 10.1 months in the resection only group (χ(2)=5.399, P=0.023). In multivariate analysis, intraoperative RFA was not an independent prognostic factor for OS and DFS (HR=0.98, 95%CI: 0.47-2.08, P=0.965; HR=1.21, 95%CI: 0.71-2.07, P=0.465). After PSM, the median OS of the resection only and the combined treatment groups were 30.2 and 25.7 months (χ(2)=0.876, P=0.350). The median DFS in the two groups was 5.3 and 4.2 months, respectively (χ(2)=0.199, P=0.650). Conclusion: In patients with similar tumor burden, liver resection combined with intraoperative RFA for unresectable CLM can achieve long-term outcomes similar to hepatectomy alone for resectable CLM.

[Basic characteristics and survival analysis of patients with hepatocellular carcinoma].

Objective: To analyze the basic characteristics of patients with hepatocellular carcinoma (HCC), and further explore the major factors affecting the prognosis of HCC patients. Methods: A total of 800 HCC patients were randomly selected from the Cancer Hospital, Chinese Academy of Medical Sciences. Their clinical and follow-up information was obtained from medical record. Univariate analysis of variance, Kaplan-Meier method and Cox regression analysis were used to analyze the patients' age at diagnosis and survival time, etc. Results: The average age of diagnosis was 55.04 years among all the 800 HCC patients, and the sex ratio of male to female was 4.48. The infection rates of HBV and HCV were 78.6% (629/800) and 5.8% (46/800), respectively. The smoking rate was 41.0% (328/800) and the alcohol consumption rate was 38.5% (328/800). 259 (32.4%) patients underwent radical treatments with liver resection as major therapy, and 541 (67.6%) patients adopted non-radical treatments with transcatheter arterial chemoembolization (TACE) as major therapy. The 1-, 3- and 5-year survival rates of the HCC patients were 73.2%, 53.7% and 42.4%, respectively. The risk factors for prognosis included alcohol abuse and treatment methods. The HR of alcohol abuse was 1.326 (95%CI: 1.058 to 1.661) and HR of treatment methods was 3.301 (95% CI: 2.483 to 4.387). Conclusions: Men account for the majority of HCC patients, and most patients have a lower age at diagnosis and adopt non-radical treatments. The exposure rates of HBV infection and alcohol abuse of HCC patients are significantly higher than those of general population. The major risk factors affecting prognosis and survival are treatments and alcohol abuse. Alcohol abuse and HBV may have synergistic effects on the survival of HCC patients.

Multi-channel poloidal correlation reflectometry on experimental advanced superconducting tokamak.

A new multi-channel poloidal correlation reflectometry is developed at Experimental Advanced Superconducting Tokamak. Eight dielectric resonator oscillators with frequencies of 12.5 GHz, 13.5 GHz, 14.5 GHz, 15 GHz, 15.5 GHz, 16 GHz, 17 GHz, and 18 GHz are used as sources. Signals from the sources are up-converted to V band using active quadruplers and then coupled together. The output waves are launched by one single antenna after passing through a 20 dB directional coupler which can provide the reference signal. Two poloidally separated antennae are installed to receive the reflected waves from plasma. The reference and reflected signals are down-converted by mixing with a quadrupled signal from a phase-locked source with a frequency of 14.2 GHz and the IF signals pass through the filter bank. The resulting signals from the mixers are detected by I/Q demodulators. The setup enables the measurement of density fluctuation at 8 (radial) × 2 (poloidal) spatial points. A coherent mode with an increasing velocity from 50 kHz to 100 kHz is observed by using the system. The mode is located in the steep gradient region of the pedestal.

Upregulation of GADD45α in light-damaged retinal pigment epithelial cells.

To better understand the molecular mechanisms responsible for light-induced damage in retinal pigmented epithelial (RPE) cells, we developed an automated device to recapitulate intense light exposure. When compared with human fibroblasts, ARPE-19 cells that had been exposed to blue-rich light-emitting diode-light of 10 000 Lux at 37 °C for 9 h displayed dramatic cellular apoptosis. Collectively, gene expression profiling and qPCR demonstrated that growth arrest and DNA damage-45α (GADD45α) expression was markedly upregulated. Transient knockdown of GADD45α partially attenuated light-damage-induced apoptosis in ARPE-19 cells, whereas GADD45α overexpression dramatically increased it. These results demonstrate the critical function of GADD45α in light-induced RPE cellular apoptosis. Quantitative reverse transcription-PCR and western blotting revealed that the upregulation of GADD45α was under direct control of p53. Moreover, treatment with Ly294002, an inhibitor of AKT phosphorylation, further promoted GADD45α gene transcription in both non-light and light-damaged ARPE-19 cells. Treatment also exacerbated RPE cellular apoptosis after light exposure, confirming that inhibition of Akt phosphorylation increases GADD45α expression. Collectively, our findings reveal that light irrigation induces human RPE cellular apoptosis through upregulation of GADD45α expression mediated through both the p53 and phosphatidylinositol 3-kinase-AKT signaling pathways. These results provide new insights into human retinal diseases elicited by light damage and open a new avenue for disease prevention and treatment.

Effect of atorvastatin on vascular endothelial function in moderately nicotine-dependent smokers.

We investigated the effect of atorvastatin on vascular endothelial function in moderately nicotine-dependent smokers. One hundred and sixty moderately nicotine-dependent smokers were randomly divided into the atorvastatin group (N = 80) and the control group (N = 80). Total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose levels, aspartate aminotransferase, total bilirubin, creatine phosphokinase, and brachial artery flow-mediated vasodilation function (FMD) were measured before and 12 months after atorvastatin treatment. After a 12-month atorvastatin therapy, the TC and LDL-C levels of patients were decreased significantly (P < 0.05) and the FMD of patients were improved significantly (P < 0.05). Compared with the control group, TC and LDL-C of the patients were significantly decreased (P < 0.05) and the FMD of the patients were significantly improved (P < 0.05). Atorvastatin may significantly improve endothelial function in moderately nicotine-dependent smokers.

[Experimental study on effect of Brucea javanica oil emulsion on rabbit intracranial pressure].

Using the method of intubation into lateral cerebral ventricle, the effect of Brucea javanica oil emulsion (BJOE) venous emulsion and oral emulsion on rabbits with normal and intracranial hypertension respectively were observed, to study whether BJOE could reduce intracranial pressure or not. The results shown that venous emulsion of BJOE had strong action against the elevation of intracranial pressure produced by SNP (P < 0.01) while oral emulsion had mild action against it, which was similar to the clinical observation exhibiting improvement of clinical manifestations after application of BJOE on intracranial hypertension caused by brain metastasis from lung cancer.

Purification and characterization of 240-kDa cGMP-dependent protein kinase substrate of vascular smooth muscle. Close resemblance to inositol 1,4,5-trisphosphate receptor.

The 240-kDa, cGMP-dependent protein kinase substrate protein obtained from porcine aortic smooth muscle, whose phosphorylation was closely associated with stimulation of plasma membrane Ca(2+)-pump ATPase (Yoshida, Y., Sun, H.-T., Cai, J.-Q., and Imai, S. (1991) J. Biol. Chem. 266, 19819-19825), was purified to near homogeneity by three successive chromatographic runs with calmodulin-, concanavalin A-, and heparin-Sepharose columns from microsomes solubilized with Triton X-100. The purified protein was found to bind inositol 1,4,5-trisphosphate (InsP3) in a specific, heparin-inhibitable manner with a Kd of 2.0 nM and Bmax of 450 pmol/mg protein (the binding of inositol 1,3,4,5-tetrakisphosphate was much weaker). In sedimentation experiments on a linear sucrose density gradient the InsP3 binding activity was always with the 240-kDa protein. Protein kinase G phosphorylated the InsP3 receptor purified from the rat cerebellum as well as the 240-kDa protein. Sialic acid content of the protein measured with Limulus polyphemus agglutinin was not significantly different from that of the cerebellar InsP3 receptor. Thus, 240-kDa protein closely resembles InsP3 receptor and may be a type of InsP3 receptor. The only difference was the behavior on SDS-polyacrylamide gel electrophoresis. The 240-kDa protein presented itself as two polypeptides with similar but slightly differing M(r) values, both of which were phosphorylated by protein kinase G.

Plasma membrane Ca(2+)-pump ATPase is not a substrate for cGMP-dependent protein kinase.

A plasma membrane Ca(2+)-pump ATPase preparation purified from porcine aorta was incubated with cGMP-dependent protein kinase (G-kinase) under the conditions under which dose-dependent stimulation of the enzyme by G-kinase was observed. Several proteins were phosphorylated, but two isoforms of plasma membrane Ca(2+)-pump ATPase with molecular masses of 135- and 145-kDa were not phosphorylated. The protein that was phosphorylated by G-kinase and identified in our previous study as the 135-kDa isoform of Ca(2+)-pump ATPase, on the basis of its almost identical mobility on SDS-PAGE, was found to be another protein with a molecular mass of 138 kDa. Fractionation of the enzyme preparation after incubation with G-kinase by a newly developed calmodulin affinity chromatographic method resulted in the separation of all the G-kinase substrates from the two isoforms of plasma membrane Ca(2+)-pump ATPase. These results suggest that the direct phosphorylation of the Ca(2+)-pump ATPase does not occur in association with the stimulation of the plasma membrane Ca(2+)-pump ATPase by G-kinase.

Cyclic GMP-dependent protein kinase stimulates the plasma membrane Ca2+ pump ATPase of vascular smooth muscle via phosphorylation of a 240-kDa protein.

The plasma membrane Ca2+ pump ATPase from porcine aorta was isolated by the calmodulin affinity chromatographic method of Kosk-Kosicka et al. (Kosk-Kosicka, D., Scaillet, S., and Inesi, G. (1986) J. Biol. Chem. 261, 3333-3338). Its activity was restored by adding either phosphatidylcholine or phosphatidylserine. Cyclic GMP-dependent protein kinase (G-kinase) stimulated the enzyme in a concentration-dependent manner. However, phosphatidylinositol kinase (PI-kinase) activity was not detected in the enzyme preparation, and the presence of phosphatidylinositol was not necessary for stimulation by G-kinase. Furthermore, adenosine, a potent PI-kinase inhibitor, did not affect the stimulation. The enzyme preparation contained three major proteins, with molecular masses of 240, 145, and 135 kDa, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The 240- and 135-kDa proteins were phosphorylated in association with the stimulation by G-kinase, but only the phosphorylation of the 240-kDa protein was dependent on the G-kinase concentration. A purified enzyme without the 240-kDa protein, prepared by our previous method (Imai, S., Yoshida, Y., and Sun, H.-T. (1990) J. Biochem. (Tokyo) 107, 755-761), was not activated by G-kinase. Immunoblotting with an antibody against the human erythrocyte Ca2+ pump revealed that the 135-kDa protein corresponded to one of the isoforms of the plasma membrane Ca2+ pump. These results suggest that the phosphorylation of the 240-kDa protein is responsible for stimulation of the plasma membrane Ca2+ pump ATPase by G-kinase.