National Medical Journal of China
Volume 95 · Issue 38 · 2015
Natl Med J China
Problems and thoughts on high-throughput sequencing detection of gene mutations in tumor targeted therapy
With the development of individualized medicine and the concept of "precision medicine", tumor targeted therapy has developed rapidly, and clinical research has gradually discovered and confirmed more gene mutations related to targeted therapy.
Surgical treatment of liver cancer beyond Barcelona staging recommendations
Primary hepatocellular carcinoma (HCC) is one of the common malignant tumors in China. Its occurrence often originates from liver cirrhosis caused by underlying liver diseases, and the degree of liver cirrhosis directly affects the treatment mode of tumor. Therefore, the factors that affect the prognosis of HCC, besides the tumor itself, should also consider the basic function of the liver. At present, there is no uniform staging system for HCC. Among them, the Barcelona Clinical Liver Cancer Staging System (BCLC) comprehensively considers liver function, tumor condition and basic physical condition, and corresponds staging with treatment and prognosis. It is recommended by the American Association for the Research of Liver Diseases (AASLD) and the European Association for the Research of Liver (EASL)[
Diagnosis, evaluation and individualized treatment of severe asthma
Through the promotion of standardized diagnosis and treatment in China, the overall control level of bronchial asthma (asthma) has been improved to a certain extent, but there are still a few patients who are still unable to achieve good control even after using high-dose inhaled glucocorticoids including combination therapy. This part of patients is usually considered to be severe asthma[
Environmental Factor Control and Asthma
In recent years, the incidence and acute exacerbation rate of bronchial asthma (asthma) have increased significantly, and the interaction between environmental factors and genetic genes is the main cause of its incidence. With the acceleration of urbanization and industrialization in China, the deterioration of environment, especially air quality, inevitably occurs, which is closely related to the occurrence and deterioration of asthma. External environmental factors include indoor and outdoor air pollution, inhaled allergens, food allergies, etc. Outdoor air pollution mainly comes from traffic pollution (such as automobile exhaust, dust, etc.) and waste after fuel combustion (such as coal or fuel oil for power generation and heating, wheat straw combustion, etc.), while indoor air pollution comes from tobacco smoke, household biofuels (cooking, heating and candles, etc.), indoor decorations and outdoor polluted air entering the room. Controlling indoor and outdoor environmental factors is an important part of asthma management.
Effects of chronic rhinitis and sinusitis on asthma control
Currently, the treatment regimen based on inhaled glucocorticoids (ICS) recommended by the Global Asthma Initiative (GINA) can achieve good or acceptable clinical control of asthma for most patients with bronchial asthma (asthma). However, some severe asthma or refractory asthma still fail to achieve basic asthma control. Expert Consensus on Diagnosis and Management of Refractory Asthma in China[
Refractory asthma with obstructive sleep apnea
Bronchial asthma is referred to as asthma. The 2014 Global Asthma Management and Prevention Strategy (GINA) mentioned in the management of refractory asthma and severe asthma that these asthma patients need to be examined for the presence of comorbidities, including chronic sinusitis, obesity, gastroesophageal reflux (GERD), obstructive sleep apnea (OSA), and other psychological and physiological diseases; The presence of comorbidities may aggravate the symptoms of asthma or make it difficult to control asthma, and it is possible to bring asthma under control by treating these comorbidities[
Focusing on individualized treatment of asthma: from phenotype to endotype
Bronchial asthma (asthma) is a heterogeneous disease[
Consensus Opinion on Multidisciplinary Diagnosis and Treatment of Acute Pancreatitis in China (Draft)
acute pancreatitis (AP) is a common clinical emergency, and its incidence is increasing year by year, especially severe AP is dangerous in onset and has a high mortality rate. The 2012 update of AP Atlanta's diagnostic criteria has attracted much attention[
Comparison of clinicopathological characteristics and prognosis of intrahepatic biliary cystic tumor between male and female patients
To describe the clinicopathological characteristics and prognosis of intrahepatic biliary cystic tumor (IBCT) and compare the difference betwwen male and female patients.
11 male and 45 female patients with histological confirmed IBCT from January 2003 to April 2014 were envolved. clinical characteristics, laboratory examination , radiological features, treatment method and prognosis were analyzed.
The mean age of male patients with IBCT was significantly older than that of female patients (54.9±10.1 years vs 46.2±12.9 years, P=0.041). There were no significant differences in radiological features between male and female patients except for mural nodules (10/11 vs 15/45, P=0.001). Intrahepatic biliary cystadenocarcinoma (IBC) was more common in male patients than female patients (8/11 vs 16/45, P=0.041). Male patients had worse prognosis than female patients (P=0.014). 1–year, 3–year, and 5–year survival of male patients was 90.9%, 45.5%, 30.3%, respectively. However, 1–year, 3–year, and 5–year survival of female patients was 94.8%, 82.7%, 78.6%.
Male patients had low incidence of IBCT, and were more common for IBC. Even with complete resection, the long–term survival was still poor, close follow–up were recommended especially for male patients.
Hepatic resection for hepatocellular carcinoma involving a single large tumor, multiple tumors or macrovascular invasion
To investigate the safety and efficacy of hepatic resection for those patients with large/multinodular hepatocellular carcinoma (HCC) or those involving macrovascular invasion (MVI).
PubMed was systematically searched for studies examining the safety and efficacy of hepatic resection for treatment of HCC involving a single large tumor (>5 cm) or multiple tumors (>2), or those involving MVI.
The identified 52 studies involving 14 922 patients that investigated the use of hepatic resection for large/multinodular HCC, and 25 studies with 4 412 patients that investigated hepatic resection for HCC with MVI. Median in–hospital mortality of patients with either type of HCC was significantly lower in Asian studies (2.7%) than in non–Asian studies (7.3%, P<0.001). Median overall survival rate was significantly higher for all Asian patients with large/multinodular HCC than for all non–Asian patients both at the time of 1 year (81% vs 65%,P<0.001) and 5 years (42% vs 32%,P<0.001). However, median overall survival rate was similar for Asian and non–Asian patients with HCC involving MVI at the time of 1 year (50% vs 52%,P=0.46) and 5 years (18% vs 15%, P=0.95). There was an increasing trend in 5–year overall survival in patients with either type of HCC.
Hepatic resection is reasonably safe and effective for the treatment of large/multinodular HCC and HCC with MVI. The available evidence argues for expanding the indications for hepatic resection in official treatment guidelines.
Protective effect of magnesium isoglycyrrhizinate combinated with verapamil on liver ischemia–reperfusion injury after semi–hepatectomy in rats
To investigate protective effect of isoglycyrrhizinate combinated with verapamil on liver ischemia–reperfusion injury after semi–hepatectomy in rats.
Male SD rats were randomly divided into five groups: false operation (group A); rats subjected to 50%hepatectomy and 45 min of hepatic ischemia(group B); rats subjected to 50%hepatectomy and 45 min of hepatic ischemia, and treated with isoglycyrrhizinate (group C); rats subjected to 50%hepatectomy and 45 min of hepatic ischemia, and treated with verapamil (group D); rats subjected to 50%hepatectomy and 45 min of hepatic ischemia, and treated with isoglycyrrhizinate and verapamil (group E). Liver function, as well as morphology, SOD activity, FasL, caspase 3, and β–catenin expression of rats were analyzed.
Compared to group B, the levels of serum ALT of group E were significantly lower (P<0.05), SOD activity of liver tissue (98.8±7.1) were significantly higher(P<0.01), pathological changes were milder, FasL gene (1.327±0.193) and protein (0.010 9±0.001 4) expression were significantly lower (P<0.01). Caspase 3 protein expression levels (0.141 0±0.005 3) were significantly lower (P<0.001), β–catenin protein expression levels (0.079 1±0.008 2) were higher significantly(P<0.01).
Isoglycyrrhizinate combinated with verapamil can effectively reduce rats liver ischemia–reperfusion injury.The protective effect on liver cells may be mediated by inhibiting apoptosis caused by Fas/FasL system, increasing β–catenin protein expression, promoting liver regeneration and relieving liver peroxidation damage.
Analysis on BK virus associated nephropathy related risk factors in renal transplant recipients
To analyze the risk factors affecting BK virus associated nephropathy(BKVAN) after kidney transplantation.
Three screening methods for BKVAN including quantitative PCR assay for BK virus(BKV) DNA load in urine and plasma and quantitative assay of urine cytology concurrently with renal transplant biopsies for the evaluation of 615 patients from January 2006 to December 2014 were used. The renal allograft biopsy specimens were analyzed by routine histologic examination, immunohistochemistry and classified into three categories of BKVAN. Potential variables were analyzed by Logistic regression model multivariate analysis to assess and rank BKVAN related risk factors.
The positive rate of urine decoy cell , BKV viruria and viremia in 615 renal recipients were 13.7%(84/615), 29.3%(180/615), and 8.8%(54/615), respectively. BKVAN were diagnosed in 49 recipients. The incidence and the median level of the number of the decoy cell, BK viral load in urine and plasma were higher in the BKVAN group than those in non–BKVAN group (all P<0.05). Tacrolimus (Tac) combined with mycophenolic acid (MPA) protocol (OR=12.4, P=0.001) and severe pneumonia post–transplant (OR=3.7, P=0.001) were the independent risk factors impacting on BKVAN in renal recipients.
The renal recipients with high level of BKV replication, whose immunosuppressant protocol include Tac and MPA, should be suspected the diagnosis of BKVAN.
Different doses of dexmedetomidine for quiet extubation during anesthesia recovery in hypertensive patients
To explore the feasibility of different doses of dexmedetomidine for quiet extubation during anesthesia recovery in hypertensive patients monitored with Narcotrend.
A total of 120 hypertensive patients scheduled for thyroid surgery from August 2012 to June 2014 in the Second Affiliated Hospital of Wenzhou Medical University, were randomly divided into 6 groups (n=20 each). Dexmedetomidine 0.4 (group M1), 0.6 (group M2), 0.8 (group M3) or 1.0 (group M4) μg·kg –1·h–1, remifentanil 0.1 μg·kg –1·min–1 (group R) and normal saline (group S) were infused for half an hour before the end of surgery, and extubation was carried out when Narcotrend index (NI) values were ≥80 in each group. Data of heart rate (HR), systolic blood pressure (SBP) and minimal alveolar concentration (MAC) of sevoflurane were observed and recorded at the time of baseline (T0), half an hour (T1) and 15 min (T2) before the end of surgery, stopping sevoflurane (T3), before extubation (T4), 1 min (T5), 5 min (T6) and 10 min(T7) after extubation. Extubation time, recovery time and related adverse reactions were also recorded.
Compared with T0, SBP and HR at T4 to T7 in four M groups were significantly lower (all P<0.05). SBP and HR at T6, T7 in group R were significantly lower than at T0 (all P<0.05). SBP at T6, T7 and HR at T4 to T7 in group R were significantly lower than that of group S (all P<0.05). SBP and HR at T4 to T7 in four M groups were significantly lower than that of group S and group R (all P<0.05). The values of MAC of sevoflurane at T2 and T3 in group R and M2–4 were significantly lower than at T1 and that of group S (all P<0.05). Recovery time in group M3 [(19.1±2.8) min] and group M4 [(20.6±4.1) min] were significantly longer compared with other four groups (allP<0.05). The percentage of cough grade at levelⅠandⅡin each M group and group R during extubation was significantly higher than that in group S (85%, 85%, 90%, 95%, 80% vs 45%, allP<0.05).
Dexmedetomidine could be safely used in hypertensive patients monitored with Narcotrend for quiet extubation during anesthesia recovery, but larger doses of dexmedetomidine may prolong the recovery time.
Risk factors for coronary artery calcification in patients with end-stage renal disease
To explore risk factors for coronary artery calcification (CAC) inpatients with end-stage renal disease (ESRD).
A total of 53 ESRD patients undergoing regular hemodialysis (3 times a week) from August 2014 to March 2015 in the Fourth Hospital of Hebei Medical University were enrolled in the study. The patients were divided into the negative control group (13 cases) and three positive groups (11 mild calcification cases, 12 moderate calcification cases and 17 severe calcification cases) based on coronary artery calcification score (CACs). Clinical data of all patients at study entry were collected. Arterial blood samples were also collected at the start of the first hemodialysis (HD) session of the week to measure the levels of serum albumin, uric acid, calcium (Ca), phosphorus (P), magnesium, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), C reactive protein(CRP), beta-2 microglobulin(β2-MG), free parathyroid hormone (iPTH), alkaline phosphatase, fibrinogen, hemoglobin (HGB) and ferritin. Meanwhile, levels of blood pH were detected after collecting pre- and post-HD blood samples to calculate ΔpH (post-HD pH subtracted pre-HD pH). Logistic regression analysis was performed to analyze the correlation of CACs with clinical data and previously-reported blood biochemical indicators, followed by analysis of the incidence of CAC and influential factors in ESRD patients.
Severity of CAC was positively correlated with age(r=0.269), HD duration (r=0.341), serum calcium (r=0.358), serum phosphorus (r=0.186) and pre-HD pH (r=0.275), but negatively correlated with serum albumin (r=–0.192) and ΔpH ( r=–0.302), all P<0.05. Logistic regression analysis revealed that age, HD duration, serum phosphorus level and ΔpH were independent risk factors for CAC in ESRD patients (P<0.05). In CAC positive groups, CAC was predominantly involved in the left anterior descending artery (P<0.05,P<0.01 andP<0.01 in mild, moderate and severe calcification group, respectively).
CAC in ESRD patients seems to be affected by multiple factors, such as age, HD duration, serum phosphorus level and ΔpH. Moreover, ΔpH affects CAC mainly by pre-HD pH. Furthermore, left anterior descending artery is predominantly affected by CAC in ESRD patients.
Analgesic effect and safety of intercostal nerve cryoanalgesia after the video–assisted thoracoscopic surgery
To investigate the analgesic efficacy and safety of intercostal nerve cryoanalgesia after video–assisted thoracoscopic surgery (VATS).
This was a prospective randomized controlled study. From May 2014 to April 2015, 80 patients who would undergoing selective surgery performed by the same surgeon team were chosen, and were randomly divided into cryoanalgesia group and intravenous analgesia group by a random number table. Visual analogue scale (VAS) at resting and movement were measured on postoperative 4 h, 1 d, 2 d, 3 d, and the amount of supplemental morphine use and adverse reactions were recorded; plasma concentration of cortisol, blood glucose, C–reactive protein (CRP) and interleukin–6 (IL–6) were detected on preoperative and postoperative 4 h, 1 d, 2 d.
Seventy–one patients with complete test process were included in the statistical analysis, including cryoanalgesia group (35 cases) and intravenous group (36 cases). No statistical differences were found in terms of age, gender, body mass index (BMI) between the two groups. VAS scores of cryoanalgesia group at movement on postoperative 4 h, 1 d, 2 d, 3 d were 5(5, 7), 4(3, 6), 3(3, 4), 3(0, 3), and in intravenous group were 5(5, 6), 5(3, 5), 3(3, 4), 2(0, 3), respectively, but there was no statistically different between two groups(P>0.05). Resting VAS scores of cryoanalgesia group on postoperative 4 h, 1 d, 2 d, 3 d were 3(2, 4), 0(0, 3), 0(0, 0), 0(0, 0), and in intravenous group were 3(0.5, 4), 2(0, 3), 0(0, 1.5), 0(0, 0) respectively, but there was no statistically different between two groups(P>0.05). Resting analgesic effectiveness (VAS≤5) of cryoanalgesia group were 91.4%, and in intravenous group were 97.2%, respectively. Median of morphine dosage was equal between two groups on postoperative 4 h, 1 d, 2 d, cumulative amount of morphine of cryoanalgesia group was higher than intravenous group, but the difference between the two groups was not statistically significant. Incidence of nausea and vomiting for intravenous group was 36.1%, significantly higher than cryoanalgesia group (17.1%, χ2=4.148, P<0.05). The change of plasma concentration of cortisol, C–response protein(CRP), interleuken–6(IL–6) was noticeable, but there was no statistical significance in each time point.
The analgesic effect of both Intercostal nerve cryoanalgesia and intravenous analgesia after VATS is almost the same.Compare with intravenous analgesia, incidence of the adverse reactions of cryoanalgesia is lower, and there is no increasing in the stress response.
Thoughts on the Carrying out International Continuing Medical Education by Oncology Society
In recent years, due to the increasing incidence of tumor, the research on oncology in all countries in the world is changing with each passing day. Continuing medical education has also become an important part of medical education. In 1972, the American Medical Association defined Continuing Medical Education ("CME") as an educational activity that meets the professional needs of physicians, patients, the public and the Medical profession, and that maintains, develops and enhances the knowledge, skills, professional qualities and interpersonal relationships of physicians[
Mechanisms of antimicrobial peptide cathelicidin secreted by non-tumorous cells for lung tumor growth
To investigate the effect of antimicrobial peptide cathelicidin secreted by non-tumorous cells in lung tumor growth.
CRAMP–/– mice and WT mice were used to establish a lung cancer model via tail vein injection of Lewis lung carcinoma cells (LLC1). Lung was weighted and tumor number on the lung surface was counted. Kaplan-Meier (K-M) survival curve was used to analyze survival rate of mice. Expression of cathelicidin, Ki-67 and CD68 in the tumor tissue was measured by immunohistochemical analysis. BALF cells were stained with Diff Quik and percentages of leukocyte types were determined by light microscopy.
Cathelicidin was high expression in inflammatory cells of tumor tissue, whereas weak expression in tumor cells. The lung weight and number of tumor in CRAMP–/– mice were (0.25±0.04)g and (9.60± 2.25), respectively, which were significantly lower than those of WT mice (0.65±0.05)g and (23.40± 2.68). The difference was statistically significant (t=6.07, 3.95, all P<0.05 ). And Kaplan-Meier survival analysis showed median survival time of CRAMP–/– mice was 49(46–51)d, which was longer than 34(28–39) d of WT mice (χ2=12.00, P<0.05). And the positive rate of Ki-67 tumor cells was significant reduced from(35.80±2.96)% in WT mice to(18.80±2.38)% in CRAMP–/– groups(t=4.48, P<0.05). The total cell number as well as the number of lymphocytes, neutrophils, and macrophages in BALFs of CRAMP–/– mice were (4.72±0.86)×104, (0.08±0.02)×104, (0.05±0.02)×104 and (4.60±0.84)×104, respectively, while of WT mice were (16.18±1.61)×104, (0.32±0.05)×104, (0.20±0.05)×104 and (15.66±1.57)×104. All of them had significant difference(t=6.28, 4.39, 3.00, 6.20, all P<0.05 ). In addition, the infiltration of macrophages into lung tumors was decreased in CRAMP–/– mice compared to WT mice, from (15.53±2.28)/high power field to (6.77±3.12)/high power field (t=3.41, P<0.05).
Non-tumor cells secreted cathelicidin promotes tumor cell proliferation and lung tumor growth. Recruitment of inflammatory cells such as macrophages into the tumor microenvironment may be the main mechanism of action.
mRNA–binding protein Human–antigen R regulates α–SMA expression in human bronchia smooth muscle cells
To investigate the role of mRNA binding protein Human–antigen R (HuR) in the over–expression of α–Smooth muscle actin (α–SMA) stimulated by Platelet–derived Growth Factor (PDGF) in cultured human bronchia smooth muscle cells.
Human bronchia smooth muscle cells cultured in vitro were divided into 0, 6, 12 and 24 h groups according to the time of PDGF treatment. Total HuR protein and total α–SMA protein expression were detected by Western blot. Total HuR mRNA and total α–SMA mRNA level were determined by quantitative real time–polymerase chain reaction. RNA interference technology was used to down–regulate HuR protein level to study the protective effect of HuR in PDGF–stimulated α–SMA protein expression.
PDGF up–regulated the expression of HuR in a time–dependent manner. The relative expression levels of whole–cell HuR protein and mRNA in 0, 6, 12, 24 h groups were 0.23±0.09, 0.42±0.11, 0.93±0.21, 1.37±0.28; 1.00±0.00, 1.09±0.03, 1.16±0.03, 1.27±0.02 (all P<0.05). The relative expression levels of α–SMA protein and mRNA in 0, 6, 12, 24 h group also showed an increase trend marked in a time–dependent manner (1.03±0.08, 1.20±0.09, 1.39±0.11, 1.58±0.10; 1.00±0.00, 1.17±0.02, 1.23±0.02, 1.45±0.03; allP<0.05). Using RNA interference technology to down–regulate HuR protein level, there was a decrease in α–SMA protein expression.
PDGF stimulation can increase the expression of HuR and α–SMA in the smooth muscle cells, and HuR protein is involved in the expression of α–SMA protein stimulated by PDGF.
Minutes of the 10th National Clinical Forum on Diagnosis and Treatment of Helicobacter Pylori and Digestive Diseases
From August 21 to 23, 2015, the 10th National Clinical Forum on the Diagnosis and Treatment of Helicobacter Pylori and Digestive Diseases, which lasted for three days, came to a close in a tense and enthusiastic, happy and exciting atmosphere in Changping District, Beijing. This forum was co-sponsored by Beijing Branch of Chinese Medical Association, Peking University First Hospital, Chinese Medical Journal and China Helicobacter Pylori Information Center. This year coincides with the 100th anniversary of the founding of Peking University First Hospital, the 100th anniversary of the founding of Chinese Medical Journal, the 10th anniversary of the founding of this forum and the anniversary of Helicobacter pylori (H.pylori) Discoverer won the Nobel Prize 10th anniversary, celebrating "Double Ten Double Hundred" together.
Case 350: Facial change – Enlargement of hands and feet – Pituitary macroadenoma – Thyroid nodule
A case of pancreaticoduodenectomy for complete visceral inversion combined with lower common bile duct carcinoma
The patient, a 70-year-old male, was admitted for 3 weeks of pain and discomfort in the middle and upper abdomen and 1 week of jaundice. Physical examination: The skin and sclera were yellow stained, and the apical pulsation point was located on the right side. Past physical fitness. Liver function showed: total bilirubin (TBIL): 121.7 μ mol/L, indirect bilirubin (IBIL): 82.6 μ mol/L. Tumor markers indicated: CA19-9>1 000 U/ml, carcinoembryonic antigen (CEA): 7.44 μ g/L. Abdominal enhanced CT showed (
Research progress of vitamin D and bronchial asthma
In recent years, the role of vitamin D outside bone metabolism has been paid attention to. Many studies have shown that vitamin D plays a certain role in the occurrence, disease severity, disease progression and drug response of asthma. The relationship between vitamin D and asthma and its related mechanisms are reviewed.
Research progress of circulating microRNA as a potential marker of cardiovascular disease
Cardiovascular disease (CVD) has become the leading cause of human death[
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