Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

Efficacy of 1 384 cases of peritoneal carcinomatosis underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

Complete cytoreductive surgery is the key to improving survival of colorectal cancer patients with peritoneal metastases: comment on PROPHYLOCHIP and PRODIGE 7 / 中华胃肠外科杂志

Peritoneal carcinomatosis (PC) is one of the difficult problems in the treatment of colorectal cancer (CRC). Based on several retrospective analyses of large samples and prospective randomized controlled studies (RCTs), NCCN and PSOGI recommend cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for selected CRC patients with mild to moderate PC. There are two important controversial issues in this field: the survival benefit of second-look surgery plus HIPEC for the patients with high risk of PC, and the specific benefit of HIPEC added to CRS for patients with PC. PROPHYLOCHIP found that second-look surgery plus HIPEC in patients at high risk of PC does not result in increased survival. PRODIGE 7 showed that overall survival (OS, 41.7 months vs. 41.2 months, P=0.99) and recurrence-free survival (RFS, 13.1 months vs. 11.1 months, P=0.43) were similar between the HIPEC group and non-HIPEC group, and suggested that HIPEC is not necessary for patients who underwent complete CRS. However, due to a series of problems in the design and implementation of this trial, the conclusion has caused great controversy and has not been widely recognized. Through detailed analysis and in-depth discussion, we believe that the benefit of HIPEC could not be denied according to PRODIGE 7. CRS + HIPEC is the embodiment and model of the concept of "Solid tumor treatment is surgery-based integrated treatment". CRS is the cornerstone of therapeutic strategies with curative intent for CRC PC and complete CRS is the key to improve the prognosis. Furthermore, HIPEC is an effective supplement to CRS.

Clinical effectiveness of photodynamic therapy combined with oral isotretinoin for moderate to severe facial acne / 中华医学美学美容杂志

Objective:To investigate the efficacy and safety of photodynamic therapy (PDT) combined with oral isotretinoin in the treatment of moderate to severe acne.Methods:Ninty patients with moderate and severe acne [42 males and 48 females; aged 18-35 (23.98±4.25)] in the Department of Dermatology, China Japan Friendship Hospital of Jilin University from January to June, 2018, were divided into three groups: PDT combined with isotretinoin group (combined group), PDT group and isotretinoin group, with 30 patients in each group. The curative effect was evaluated on the 30th and 60th day of the treatment and the follow-up was carried out regularly.Results:At 10, 20, and 30 days of the treatment, the clearance rates of non-inflammatory skin lesions and total skin lesions were better than that of the PDT group; the clearance rates of inflammatory, non-inflammatory and total skin lesions in the combined group were better than those of the isotretinoin group. At 30 days of treatment, the efficacy of the combined group was better than that of the PDT group (χ 2=13.169, P<0.05) and isotretinoin group (χ 2=19.606, P<0.05). The treatment course of the combined group was shorter than that of the PDT group ( P<0.05). Six months after the treatment, the recurrence rate of the combined group was lower than that of the isotretinoin group (χ 2=4.941, P<0.05). And there was no significant difference of the incidence of adverse reactions between the above two groups ( P>0.05). Conclusions:The combination of photodynamic therapy and oral isotretinoin therapy for moderate to severe acne can improve the efficacy, shorten the course of treatment, and reduce the recurrence rate and adverse reactions, which provides a new idea for the treatment of acne.

Miltirone induces cell death in hepatocellular carcinoma cell through GSDME-dependent pyroptosis

Pyroptosis is a form of programmed cell death, and recently described as a new molecular mechanism of chemotherapy drugs in the treatment of tumors. Miltirone, a derivative of phenanthrene-quinone isolated from the root of Bunge, has been shown to possess anti-cancer activities. Here, we found that miltirone inhibited the cell viability of either HepG2 or Hepa1-6 cells, and induced the proteolytic cleavage of gasdermin E (GSDME) in each hepatocellular carcinoma (HCC) cell line, with concomitant cleavage of caspase 3. Knocking out switched miltirone-induced cell death from pyroptosis to apoptosis. Additionally, the induction effects of miltirone on GSDME-dependent pyroptosis were attenuated by siRNA-mediated caspase three silencing and the specific caspase three inhibitor Z-DEVD-FMK, respectively. Miltirone effectively elicited intracellular accumulation of reactive oxygen species (ROS), and suppressed phosphorylation of mitogen-activated and extracellular signal-regulated kinase (MEK) and extracellular regulated protein kinases 1/2 (ERK1/2) for pyroptosis induction. Moreover, miltirone significantly inhibited tumor growth and induced pyroptosis in the Hepa1-6 mouse HCC syngeneic model. These results provide a new insight that miltirone is a potential therapeutic agent for the treatment of HCC GSDME-dependent pyroptosis.

Impact of different operative approaches for laparoscopic pancreaticoduodenectomy on short-term treatment outcomes / 中华肝胆外科杂志

Objective:To study the impact of traditional versus artery first approach in laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 58 patients who underwent laparoscopic pancreaticoduodenectomy using the two different approaches from February 2016 to August 2018 at the Xianyang Central Hospital affiliated to Xi'an Jiaotong University Medical Department were retrospectively analyzed.Results:All 58 patients successfully underwent the complete laparoscopic Whipple operation using the Child digestive tract reconstruction and anastomosis. There was no conversion to laparotomy. The average operation times for the conventional approach group (35 cases) was (302.0±20.0) min and the digestive tract reconstruction time was (36.0±15.0) min. The intraoperative blood loss was (365.0±150.0) ml. Negative pathological resection margins on intraoperative frozen section examination were achieved in 33 patients. Early postoperative complications happened in 6 patients which included grade A pancreatic fistula in 3 patients (1 patient complicated with biliary fistula and 1 patient complicated with gastric emptying disorder), and grade B pancreatic fistula in 2 patients who were complicated with abdominal hemorrhage, successfully treated by conservative treatment. Postoperative pathological examination showed that 32 patients (91.4%) had R 0 resection and 3 patients (8.6%) had R 1 resection. The number of lymph node dissection was (7.5±5.5). On the other hand, the average operation time of the artery first access group (23 cases) was (355.0±25.0) min, and the reconstruction time of digestive tract was (41.0±12.0) min. The amount of bleeding was (410.0±200.0) ml. During the operation, 22 patients had negative resection margins shown on pathological frozen sections. Early postoperative complications occurred in 3 patients, including 1 patient with grade A pancreatic fistula which was complicated with gastric emptying disorder, and 2 patients with grade B pancreatic fistulas which were complicated with abdominal hemorrhage. The patients were successfully managed by conservative treatment. Postoperative pathological examination showed that 22 patients (95.7%) had R 0 resection and 1 patient (4.3%) R 1 resection. The number of lymph node dissection was (6.8±4.2). Conclusion:The LPD surgical approach was selected according to the general conditions of patients, locations of tumors, relationship of tumors with blood vessels, and technical skills of surgeons with the aims to achieve adequate lesion clearance, organ protection, damage control, and safety and efficiency of minimally invasive surgery.

Laparoscopic versus open splenectomy plus portaazygous devascularization in the treatment of patients with portal hypertension with recurrent upper gastrointestinal bleeding / 中华肝胆外科杂志

Objective To compare the efficacies of laparoscopic versus open splenectomy plus portaazygous devascularization in the treatment of patients with portal hypertension with recurrent upper gastrointestinal bleeding.Methods The clinical data of patients who underwent laparoscopic (n =60) versus open (n =52) splenectomy plus open portaazygous devascularization in the Department of Hepatobiliary Surgery,the Center Hospital of Xianyang City,Xi'an Jiaotong University Health Science Center from March 2014 to February 2017 were retrospectively analyzed.Results There was no perioperative death in the 2 groups.The amounts of intraoperative bleeding,the durations of the operation,the time of first flatus passed after operation and the duration of postoperative hospitalization were compared,and the differences were significantly different (t =3.288,2.533,3.325,2.823,P ＜ 0.05).There was no significant difference in the total hospitalization expenses (t =0.651,P ＞0.05).The incidence of postoperative complications was significantly higher in the open surgery group (x2 =7.622,P ＜ 0.05).At 1-month after surgery,color doppler flow imaging (CDFI) showed no significant difference on the portal blood flow between the two groups (t =0.625,P ＞ 0.05).On gastroscopy,the esophageal and gastric varices were significantly improved,and there was no significant difference between the two groups (x2 =0.718,P ＞ 0.05).Liver function was better in the laparoscopic group than the open group (x2 =3.765,P ＜ 0.05).Comparison of the rebleeding rates and the incidences of hepatic encephalopathy for the two groups at 1 year after operation showed significantly better outcomes for the laparoscopic group (x2 =2.351,1.245,P ＜ 0.05).The 1-year and 3-year survival rates after operation (x2 =0.218,0.361,P ＞ 0.05) were not significantly different.Conclusion Compared with laparotomy,laparoscopic splenectomy plus portaazygous devascularization had the advantages of less trauma,better short-term and long-term efficacies.

Analysis of risk factors for acute kidney injury following hepatic arterial chemoembolization inpatientswithhepatocellularcarcinomaofChildclassA / 中华放射学杂志

Objective To explore the incidence and risk factors of acute kidney injury (AKI) following hepatic arterial chemoembolization inpatients with hepatocellular carcinoma(HCC),Child class A. Methods Retrospective analysis was performed on patients with HCC,Child Class A who were admitted from January 2008 to October 2016.The inclusion criteria:(1) patients were diagnosed with pathologically confirmed hepatocellular carcinoma based on the standards of primary liver cancer diagnosis and treatment (2011 edition);(2) patients have complete laboratory parameters and imaging data within the 7 days before the TACE treatment;(3) the Child-pugh score was 5 to 6;(4) patients have no acute or chronic renalfailure before the treatment of TACE.The morbidity of AKI after TACE was investigated.Twenty-six factors such as age,sexy,contrast dose,hemoglobin were included as independent variable, so as to investigate the risk factors for postoperative AKI. Results A total of 818 patients were included in the study, including 38 experiencing postoperative AKI(4.64%).Multivariate logistic regression analysis identified elevated preoperative uric acid as the independent risk factor for postoperative AKI(OR=1.005,95% CI 1.000 to 1.009,P=0.037), and elevated preoperative hemoglobin as the protective factor for postoperative AKI(OR=0.974,95% CI 0.952 to 0.997,P=0.028).Conclusions AKI is not uncommon following hepatic arterial chemoembolization inpatients with HCC,Child Class A,and is correlated with elevated uric acid and anemia.Preoperative risk assessment and anemia correction might be effective for reducing the incidence of AKI following hepatic arterial chemoembolization.

Total laparoscopic surgery vs open surgery in the treatment of gallbladder carcinoma / 中华普通外科杂志

Objective To investigate the therapeutic effect of total laparoscopic vs open surgery for gallbladder carcinoma.Methods Clinical data of 51 cases of laparoscopic surgery and 41 cases of open operation for gallbladder cancer from Mar 2012 to Dec 2016 were analyzed retrospectively.Results There were no perioperative death in both groups.The blood loss during operation,operative time,the first anal exhaust after operation and the hospital stay were in favour of laparoscopic procedure (t =2.756,2.325,1.362,2.252,P ＜ 0.05).There was no significant difference in total hospitalization expenses (t =0.655,P ＞ 0.05),the short-term postoperative complications were in favor for laparoscopic surgery (x2 =5.522,P ＜ 0.05).The 1,3,5-year survival rates of laparoscopic group and laparotomy group were comparable (x2 =0.356,0.428,0.388,P ＞0.05).Conclusion Laparoscopic radical surgery for gallbladder cancer is safe,feasible and less traumatic than open surgery,with long term survival comparable to open surgery.

Diagnostic potential of Dickkopf-1 for heptocellular carcinoma using magnetic solid phase chemiluminescent immunoassay / 国际检验医学杂志

Objective This is the first study to explore clinical application value of serum Dickkopf-1 (DKK-1) detection in diagnosis of heptocellular carcinoma (HCC) by magnetic solid phase chemiluminescent immunoassay.Methods The level of serum DKK-1 and AFP in 205 cases of HCC,40 cases of liver cirrhosis,and 200 cases of healthy control were quantitatively detected by Magnetic solid phase chemiluminescent immunoassay.The area under ROC curve,sensitivity and specificity of DKK-1 and AFP for diagnosing HCC were calculated.Results The serum level of DKK-1 in HCC group was significantly higher than those of the liver cirrhosis group and healthy control group (P<0.01).DKK-1 maintained diagnostic sensitivity for patients with HCC who were alpha-fetoprotein (AFP) negative (66.3%).ROC curves showed optimum diagnostic cut-off value was 2.4 ng/mL,area under curve (AUC) was 0.822 (95% CI:0.783-0.856),sensitivity 65.9%,and specificity 87.5%).Moreover,measurement of DKK1 and AFP together improved diagnostic accuracy for HCC versus all controls compared with either test alone [AUC 0.915,95%CI:0.886-0.940),sensitivity 81.5 %(P<0.05)].Conclusion Serum DKK-1 detection has an important clinical value for diagnosis of HCC,especially for HCC with AFP negative.The combined detection of serum DKK-1 and AFP can greatly increase sensitivity and accuracy for diagnosing HCC.

Clinical effect of laparoscopic improved ileal bypass surgery for treatment of type 2 diabetes mellitus / 中华内分泌外科杂志

Objective To explore the clinical efficacy of laparoscopic improved ileal bypass (LIB)for treatment of type 2 diabetes mellitus(T2DM).Methods The clinical data of 52 patients who received LIB for T2DM at the Center Hospital Xianyang City,Southern Medical University,from May.2012 to Jul.2015 were retrospectively analyzed.On the basis of their body mass index (BMI),all cases were divided into two groups:group A (16 cases,BMI≥28 kg/m2) and group B(36 cases,BMI ＜28 kg/m2).LIB surgery were complete by laparoscopic ultrasound knife and the cutting anastomat etc.Before and during one year after surgery fasting blood glucose(FBG),fasting c-peptide,glycosylated hemoglobin (HbA1c) and BMI were detected to evaluate the outcome of T2DM.Count data and comparison of rates were analyzed by chi-square test.Measurement data with normal distribution were presented as ±s and analyzed by the t test.Repeated measurement data were analyzed by the repeated measuresanalysis of variance.Results All the 52 patients underwent successful LIB without perioperative death during the follow-up of 12 months.There were significant differences in FBG and HbA1c at admission and 12 months after surgery:group A (t=4.223,3.602,P＜0.05);group B (t=4.356,5.613,P＜0.05).With reference to the literature[1] curative effect evaluation standard,13 patients had complete remission,2 patients had partial remission and 1 patient had non-remission in group A,accounting for 81.25％,12.5％,and 6.25％ respectively.For 36 patients in group B,32 patients had complete remission,3 patients had partial remission and 1 patient had non-remission,accounting for 88.9％,8.3％,and 2.8％ respectively.Total treatment effectiveness was 96.2％ (50/52).No significant differences was found between group A and group B at 12 months after surgery (X2=0.053,P＞0.05).BMI at admission and 12 months after surgery had no significant differences in group A (t=1.581,P＞0.05),nor group B(t=2.124,P＞0.05).Conclusions LIB for T2DM improved the glucose metabolism significantly,with unconspicuous influence for BMI and was indications for the non-obese T2DM.Due to the poor weight loss,LIB choose carefully in obese patients with T2DM.The therapy has small trauma,fewer complications,simple operation skills and facilitated clinical promotion.

Comparative analysis of modified instruments and conventional instruments in transumbilical single-pore laparoscopic cholecystectomy / 中国医师进修杂志

Objective To analyze the effect of clinical application of transumbilical single-pore laparoscopic cholecystectomy with modified instruments and conventional instruments. Methods Fifty transumbilical single-pore laparoscopic cholecystectomy patients with conventional instruments (conventional instruments group) and 50 transumbilical single-pore laparoscopic cholecystectomy patients with modified instruments (modified instruments group) were selected. The operation time, recovery satisfaction degree of navel incision, intraoperative bleeding, postoperative complication, change rate of surgical procedure, length of hospital stay and hospitalization expenses were compared between 2 groups. Results The operation time and change rate of surgical procedure in modified instruments were significantly lower than those in conventional instruments, and the recovery satisfaction degree of navel incision was significantly higher than that in conventional instruments:(43.5 ± 12.0) min vs. (60.0 ± 2.2) min, 2.0% (1/50) vs. 12.0% (6/50) and (4.5 ± 0.2) scores vs. (3.2 ± 1.2) scores, and there were statistical differences (P0.05). Conclusions The transumbilical single-pore laparoscopic cholecystectomy with modified instruments can obviously reduce the operation time and the change rate of surgical procedure, improve the recovery satisfaction degree of navel incision, reduce the operation difficulty of performer and shorten the time of learning curve.

Research status of targeted drug and whole brain radiotherapy for non-small cell lung cancer with brain metastasis / 国际肿瘤学杂志

Whole brain radiation therapy has become the standard treatment of non-small cell lung cancer (NSCLC) with brain metastasis,because it prolongs the survival times of NSCLC patients with brain metastases.The emergence of molecular targeted drugs is a major innovation in the traditional sense of the cancer treatment.Molecular targeted drugs have many advantages such as convenient dosing,rapid onset,improving the intracranial and extracranial tumor lesions at the same time,mild adverse reactions and good tolerance,which provide a new and better choice for the treatment of NSCLC patients with brain metastases.

Hepatocellular adenoma with malignant transformation in male patients with non-cirrhotic livers / 癌症

<p><b>INTRODUCTION</b>Hepatocellular adenomas (HCAs), with a risk of malignant transformation into hepatocellular carcinoma (HCC), classically develop in young women who are taking oral contraceptives. It is now clear that HCAs may also occur in men. However, it is rarely reported that HCAs with malignant transformation occur in male patients with non-cirrhotic livers. This study aimed to characterize the malignancy of HCAs occurring in male patients.</p><p><b>METHODS</b>All patients with HCAs with malignant transformation who underwent hepatectomy at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 1, 1999 and December 31, 2011 were enrolled in the study. The clinical characteristics as well as radiologic and pathologic data were reviewed.</p><p><b>RESULTS</b>HCAs with malignant transformation were observed in 5 male patients with non-cirrhotic livers, but not in female patients. The alpha-fetoprotein (AFP) levels were higher in patients with HCAs with malignant transformation than in patients with HCAs without malignant transformation. The diameters of the tumors with malignant transformation were larger than 5 cm in 3 cases and smaller than 5 cm in 2 cases. The 5 patients were all alive without recurrence by the end of the study period. The disease-free survival times of the 5 patients were 26, 48, 69, 69, and 92 months.</p><p><b>CONCLUSION</b>Our results indicate that resection would be advised even if the presumptive diagnosis is adenoma smaller than 5 cm in diameter, especially in male patients.</p>

Regulative effects of vessel active drugs on extremital skin temperature of experimental animals exposed to cold / 中国应用生理学杂志

<p><b>OBJECTIVE</b>Using an experimental model of animals exposed to cold to evaluate the regulative effects of prazosin hydrochloride (Pra) and racanisodamine (Ani) on extremital skin temperature of rats and mice.</p><p><b>METHODS</b>Eighty animals were randomly divided into eight groups according to the drug dosage. After been administered with drugs by intragastric at room temperature for 60 min, the animals were moved into specified temperature (5 degrees C,18 degrees C) environment and the skin temperatures at the 1/3 site at the proximal end of tail were measured by infrared camera on 180 min and 300 min. Effects of drug were evaluated by changes in tail skin temperatures.</p><p><b>RESULTS</b>Pra and Ani combination raised the extremital skin temperature of experimental animals significantly in a dose-dependent manner, while single use of Pra was not potent to rats and less potent to mice, and single use of Ani could not raise extremital skin temperature of both rats and mice. Change of rectal temperature in mice showed that Pra and Ani combination did not affect core temperature.</p><p><b>CONCLUSION</b>Pra and Ani combination could significantly raise extremital skin temperature of rats and mice exposed to cold, and would not affect their core (rectal) temperature.</p>

DS147 improves pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation / 华中科技大学学报（医学）（英德文版）

The study examined the effect of DS147, the bioactive component of the traditional herbal recipe Bangdeyun, on pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation (COS), and the underlying mechanisms. Female mice were superovulated by intraperitoneal injection of 7.5 IU of pregnant mare serum gonadotropin (PMSG) followed by an additional injection of 7.5 IU hCG 48 h later to establish embryo implantation dysfunction (EID) model. Pregnant mice were randomly divided into normal control group, COS group and DS147-treated groups. The pregnancy rate and the average implantation site were obtained on pregnancy day 8 (PD8). The side effect of 200 mg/kg of DS147 on naturally pregnant mice was also observed. Further, the uterine and ovarian tissue samples were collected on PD5 for measuring their weights, observing the development of the endometrium and ovary, and detecting the endometrial expression of MMP-2, TIMP-2, CD34 and angiogenin (ANG). The female mice treated with DS147 at doses of 100 to 800 mg/kg showed a higher pregnancy rate than those in COS group, and the highest pregnancy rate of 83.3% occurred in the 200 mg/kg DS147-treated group. Moreover, no obvious side effect was found in mice treated with 200 mg/kg DS147 on PD8 and PD16. The ovarian and uterine weights, and the expression levels of MMP-2, ANG and CD34 were significantly increased in DS147-treated groups when compared with COS group. The TIMP-2 expression level was much lower in DS147-treated mice than in COS mice and the ratio of MMP-2/TIMP-2 was much higher in DS147-treated group than in COS group, and even higher than normal control group. In all, these findings suggest that DS147 may improve pregnancy in mice with COS-induced EID by promoting matrix degradation and angiogenesis, and improving the development of corpus luteum and endometrial decidualization around the implantation window.

DS147 improves pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation / 华中科技大学学报（医学）（英德文版）

The study examined the effect of DS147, the bioactive component of the traditional herbal recipe Bangdeyun, on pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation (COS), and the underlying mechanisms. Female mice were superovulated by intraperitoneal injection of 7.5 IU of pregnant mare serum gonadotropin (PMSG) followed by an additional injection of 7.5 IU hCG 48 h later to establish embryo implantation dysfunction (EID) model. Pregnant mice were randomly divided into normal control group, COS group and DS147-treated groups. The pregnancy rate and the average implantation site were obtained on pregnancy day 8 (PD8). The side effect of 200 mg/kg of DS147 on naturally pregnant mice was also observed. Further, the uterine and ovarian tissue samples were collected on PD5 for measuring their weights, observing the development of the endometrium and ovary, and detecting the endometrial expression of MMP-2, TIMP-2, CD34 and angiogenin (ANG). The female mice treated with DS147 at doses of 100 to 800 mg/kg showed a higher pregnancy rate than those in COS group, and the highest pregnancy rate of 83.3% occurred in the 200 mg/kg DS147-treated group. Moreover, no obvious side effect was found in mice treated with 200 mg/kg DS147 on PD8 and PD16. The ovarian and uterine weights, and the expression levels of MMP-2, ANG and CD34 were significantly increased in DS147-treated groups when compared with COS group. The TIMP-2 expression level was much lower in DS147-treated mice than in COS mice and the ratio of MMP-2/TIMP-2 was much higher in DS147-treated group than in COS group, and even higher than normal control group. In all, these findings suggest that DS147 may improve pregnancy in mice with COS-induced EID by promoting matrix degradation and angiogenesis, and improving the development of corpus luteum and endometrial decidualization around the implantation window.

The damage effects of hypothermia combined with hypoxia on rat pulmonary microvascular endothelial cells / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the synergistic effects of hypothermia and hypoxia on the damage of pulmonary microvascular endothelial cells (PMVEC) in rat.</p><p><b>METHODS</b>Primary PMVECs were obtained by complex phosphoesterasum digesting from isolated lung tissues of Wistar rats, the PMVECs were identified by phase contrast microscope and immunofluorescence studies for CD31 antigen and bandeiraea simplicifolia isolectin (BSI) binding test. Factorial design was adopted in trial according to hypothermia and hypoxia existing or not. Using corresponding kit measured the levels of lactate dehydrogenase (LDH) activity in cell medium. Level of nitric oxide (NO) concentration was measured by Griess Assay. RT-PCR was used to examine the expression of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) mRNA in PMVECs.</p><p><b>RESULTS</b>The monolayer of cultured PMVECs displayed the shape of pavingstone. CD31 antigen and binding BSI results by fluorescence microscope identified the cultured cells were PMVECs. Compared to the control group, LDH activity and VEGF, ET-1 expression levels were significantly increased in hypothermia group, hypoxia group and hypoxia combined with hypothermia group. And the levels of NO concentration were reduced in these three groups. The results of One-way ANOVA showed that there was a synergistic effect between hypothermia and hypoxia.</p><p><b>CONCLUSION</b>Hypothermia and hypoxia both have an effect on PMVECs whether in altering the cell permeability or in releasing of vasoactive substances including NO and ET-1. In addition, there is a synergistic effect between hypothermia and hypoxia.</p>

Effects of low temperature exposure on dermal microvascular endothelial cells function / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the damage effects and expression of vascular endothelial growth factor (VEGF) exposed with different low-temperatures on rat dermal microvascular endothelial cells (DMVECs).</p><p><b>METHODS</b>Primary DMVECs were obtained by discontinuous Percoll gradient centrifugation. The DMVECs were identified by phase contrast microscope and immunofluorescence studies for CD31 antigen. Applied 28 degrees C, 12 degrees C and 0 degrees C to interfere with rat DMVECs as cold-exposure model. The changes of cells morphology were observed under invert microscope. The membrane integrity was determined by lactate dehydrogenase (LDH) activity. RT-PCR was used to examine the expression of vascular endothelial growth factor mRNA in cells.</p><p><b>RESULTS</b>The monolayer of cultured PMVECs displayed the shape of pavingstone. CD31 antigen and binding BSI results by fluorescence microscope identified the cultured cells were DMVECs. After 24 h cold exposure, the cell morphology of 0 degrees C group was shrunken, the other groups were "Fibroblast-like". The LDH activity (U/L) in the medium of 28 degrees C, 12 degrees C and 0 degrees C groups was 54.17 +/- 3.02, 64.66 +/- 3.03, 82.13 +/- 10.91 respectively, which was significantly higher than that of 37 degrees C group (12.23 +/- 3.0, P < 0.01). The VEGF mRNA expression level was up-regulated in 28 degrees C group and 12 degrees C group versus control group (P < 0.05), but unchanged in 0 degrees C group.</p><p><b>CONCLUSION</b>The rat DMVECs injury severity are deteriorated with temperature decreasing, and VEGF might be involved in the regulation of membrane permeability in this period.</p>

Development of sleep/wake patterns in infants during the first 12 months of life / 中华儿科杂志

<p><b>OBJECTIVE</b>This was a nationwide study of sleep circadian in term infants. The aim was to understand the development characteristics of infants' sleep/wake patterns longitudinally in their own home environments over the first 12 months of life.</p><p><b>METHOD</b>Totally 524 healthy term infants from 9 urban districts took part in this project Their sleep/wake patterns over 24 h were recorded using parental sleep diaries, from the 2nd day to 12 months old.</p><p><b>RESULT</b>The results showed that infant daytime sleep changed significantly at 0-2, 3-4, 5-6, and 8-9 months after birth, and the change was the fastest in the first month, the mean percentage of daytime sleep decreased from 82.4% at Day 2 to 62.8% at 1 month old. Also, the average number of naps reduced from 3.7 to 2 across the infancy. The ability of continuous sleep throughout the night gradually enhanced from 1 month old, and the nocturnal longest sleep time extended to 6.8 h at 4 months of age as well as the nighttime awakening frequency less than 0.5 over 6 months old. Additionally, the nighttime sleep increased significantly at 4 and 9 months after birth, where the proportion of nighttime sleep increased from 55.8% at Day 2 to 64.3% of 4 months and 71.2% of 9 months respectively. In general, the total sleep time over a 24 h period presented a downward trend as the infant aged.</p><p><b>CONCLUSION</b>The periods 0-6 and 8-9 months after birth were the key periods for the development of infant sleep.</p>