CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules / 中国肺癌杂志

BACKGROUND@#Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules.@*METHODS@#122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed.@*RESULTS@#Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples.@*CONCLUSIONS@#CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.

Changes of plasma high density lipoprotein cholesterol and metabolic indicators in obese patients after laparoscopic sleeve gastrectomy / 中华消化外科杂志

Objective:To investigate the changes of plasma high density lipoprotein cholesterol (HDL-C) and metabolic indicators in obese patients after laparoscopic sleeve gastrectomy (LSG).Methods:The retrospective cohort study was conducted. The clinical data of 69 obese patients who were admitted to the Tenth People′s Hospital of Tongji University from August 2013 to March 2017 were collected. There were 32 males and 37 females, aged (33±12)years, with a range from 18 to 65 years. Of 69 patients, 44 patients with preoperative HDL-C concentration <1.04 mmoL/L were allocated as low HDL-C group, and 25 patients with preoperative HDL-C concentration ≥1.04 mmoL/L were allocated as normal HDL-C group. Sixty-nine patients underwent LSG. Observation indicators: (1) analysis between preoperative HDL-C and clinical indicators; (2) follow-up; (3) stratified analysis of plasma HDL-C. Follow-up was conducted using outpatient examination and hospitalization review to detect changes of plasma HDL-C, insulin resistance index, uric acid, free fatty acids and body mass every 3 months after operation up to September 2017. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M ( P25, P75), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Pearson correlation coefficient was used to analyze measurement data with normal distribution, and Spearman correlation was used to analyze measurement data with skewed distribution. Repeated measurement data were analyzed by ANOVA. Results:(1) Analysis between preoperative HDL-C and clinical indicators: results of correlation analysis showed that the preoperative plasma HDL-C concentration was negative correlated with the body mass, height, abdominal circumference, insulin resistance index and triglyceride in 69 patients ( r=-0.246, -0.307, -0.262, -0.253, -0.301, P<0.05), and the preoperative plasma HDL-C concentration was not correlated with the age, body mass index (BMI), fasting blood glucose, glycosylated hemoglobin, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, uric acid, creatinine, free fatty acid, fasting serum insulin, total cholesterol and low density lipoprotein cholesterol ( P>0.05). The preoperative plasma HDL-C concentration was still negative correlated with the body mass in 69 patients after adjusting for age, BMI, fasting blood glucose, glycosylated hemoglobin, fasting serum insulin and insulin resistance index ( r=-0.277, P<0.05). (2) Follow-up: 69 patients were followed up postoperatively for 6 months (6 months, 12 months). The plasma HDL-C concentration, insulin resistance index, uric acid, free fatty acids, body mass of low HDL-C group at postoperative 3 and 6 months were (0.96±0.18)mmol/L, 2.20(0.51, 11.66), (411±93)μmol/L, 0.57 mmol/L (0.20 mmol/L, 1.00 mmol/L), (92±18)kg and (1.11±0.18)mmol/L, 2.19(0.71, 8.75), (389±100)μmol/L, 0.40 mmol/L(0.13 mmol/L, 1.10 mmol/L), (86±17)kg, respectively. The above indicators of normal HDL-C group at postoperative 3 and 6 months were (1.17±0.24)mmol/L, 2.22(0.24, 7.04), (379±105)μmol/L, 0.60 mmol/L(0.27 mmol/L, 1.10 mmol/L), (84±16)kg and (1.34±0.20)mmol/L, 1.60(0.36, 5.56), (359±92)μmol/L, 0.42 mmol/L (0.16 mmol/L, 2.90 mmol/L), (80±18)kg, respectively. There was significant difference in the changes of postoperative plasma HDL-C concentration between the two groups ( F=41.443, P<0.05), and there was interaction between groups and time points ( F=6.252, P<0.05). There was significant difference between different time points ( F=29.900, P<0.05). There was significant difference in the changes of postoperative insulin resistance index between the two groups ( F=4.313, P<0.05), and there was no interaction between groups and time points ( F=2.298, P>0.05). There was significant difference between different time points ( F=29.800, P<0.05). There was no significant difference in the changes of postoperative uric acid between the two groups ( F=1.669, P>0.05), and there was no interaction between groups and time points ( F=0.111, P>0.05). There was significant difference between different time points ( F=12.796, P<0.05). There was significant difference in the changes of postoperative free fatty acids between the two groups ( F=5.465, P<0.05), and there was no interaction between groups and time points ( F=0.504, P>0.05). There was no significant difference between different time points ( F=1.405, P>0.05). There was significant difference in the changes of postoperative body mass between the two groups ( F=5.614, P<0.05), and there was no interaction between groupsand time points ( F=2.174, P>0.05). There was significant difference between different time points ( F=497.496, P<0.05). (3) Stratified analysis of plasma HDL-C. ① Changes of postoperative plasma HDL-C in obese patients of different genders: of 69 patients, the plasma HDL-C concentration of the 32 male patients before operation and at postoperative 3 and 6 months were (0.91±0.19)mmol/L, (1.02±0.24)mmol/L, (1.18±0.23)mmol/L, respectively, and the percentage increase of plasma HDL-C concentration at postoperative 3 and 6 months were 12.00%(4.00%, 12.00%)and 20.00%(12.00%, 39.25%), respectively. The above indicators of the 37 female patients were (1.05±0.21)mmol/L, (1.06±0.22)mmol/L, (1.22±0.22)mmol/L and 0(-9.50%, 8.25%), 12.00%(2.00%, 23.00%), respectively. There was significant difference in the changes of percentage increase of plasma HDL-C concentration between the male and female patients ( F= 6.716, P<0.05), and there was interaction between groups and time points ( F=3.861, P<0.05). There was significant difference between different time points ( F=37.374, P<0.05). ② Changes of postoperative plasma HDL-C in obese patients of different genders in low HDL-C group and normal HDL-C group: of 44 patients in low HDL-C group, the plasma HDL-C concentration of the 24 male patients before operation and at postoperative 3 and 6 months were (0.82±0.12)mmol/L, (0.99±0.21)mmol/L, (1.12±0.22)mmol/L, respectively, and the percentage increase of plasma HDL-C concentration at postoperative 3 and 6 months were 16.00%(-1.75%, 28.75%) and 27.50%(15.75%, 43.50%), respectively. The above indicators of the 20 female patients in low HDL-C group were (0.89±0.08)mmol/L, (0.93±0.14)mmol/L, (1.10±0.14)mmol/L and 1.50%(-8.25%, 16.50%), 18.00%(9.00%, 23.00%), respectively. There was significant difference in the changes of percentage increase of plasma HDL-C concentration between the male and female patients ( F=4.503, P<0.05), and there was interaction between groups and time points ( F=3.594, P<0.05). There was significant difference between different time points ( F=37.096, P<0.05). Of 25 patients in normal HDL-C group, the plasma HDL-C concentration of the 8 male patients before operation and at postoperative 3 and 6 months were (1.15±0.12)mmol/L, (1.12±0.32)mmol/L, (1.32±0.21)mmol/L, respectively, and the percentage increase of plasma HDL-C concentration at postoperative 3 and 6 months were -1.00%(-14.00%, 12.00%), 13.50%(6.75%, 32.50%), respectively. The above indicators of the 17 female patients in normal HDL-C group were (1.23±0.16)mmol/L, (1.20±0.20)mmol/L, (1.36±0.20)mmol/L and 0(-13.75%, 4.25%), 5.50%(0, 28.50%), respectively. There was no significant difference in the changes of percentage increase of plasma HDL-C concentration between the male and female patients ( F=0.209, P>0.05), and there was no interaction between groups and time points ( F=0.176, P>0.05). There was significant difference between different time points ( F=6.481, P<0.05). Conclusions:For patients with low or normal plasma HDL-C concentration preoperative, there are significant differences in the changes of HDL-C, insulin resistance index, free fatty acids and body mass after LSG. There is significant difference in the changes of postoperative percentage increase of plasma HDL-C concentration between male and female patients who with low plasma HDL-C concentration preoperative.

Effects of laparoscopic sleeve gastrectomy on insulin secretion patterns in morbidly obese patients / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To assess the effects of laparoscopic sleeve gastrectomy (LSG) on insulin secretion mode and metabolism of glucose and lipid in morbidly obese patients.</p><p><b>METHODS</b>Clinical data of 65 morbidly obese patients [body mass index (BMI) ≥30 kg/m] undergoing LSG at Shanghai 10th People's Hospital from August 2012 to December 2016 were retrospectively analyzed. According to the result of OGTT, these obese patients were divided into three groups: normal glucose tolerance (NGT, 23 cases), impaired glucose tolerance (IGT, 22 cases) and type 2 diabetes mellitus (DM, 20 cases) groups. Twenty-two healthy people [BMI (23.1±1.4) kg/m] were used as control group. The anthropometries parameters [weight, BMI, waist circumference, body fat percentage, excess weight loss(%EWL)], glucose metabolic indices [fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), homeostasis model assessment-insulin resistance index (HOMA-IR)], lipid profile (TC, TG, HDL-C, LDL-C) and inflammatory factor (UA, TNF-α) of 3 groups were detected before operation and at postoperative 1-, 3-, 6-month. These variables were analyzed among morbidly obese groups before and after surgery and compared to control group. Clinical registration number of this study was ChiCTROCSl2002381.</p><p><b>RESULTS</b>Body weight, waist circumference and BMI of morbidly obese patients all decreased at postoperative 1-, 3-, 6-month. Postoperative %EWL increased obviously to (71.5±24.7)% with the highest range in DM group. Percentage of successful weight loss (%EWL>50%) in NGT, IGT and DM groups was 63.6%, 83.9% and 90.0% at postoperative 6-month respectively, and DM group was also the highest. At postoperative 6-month, HbA1c of 3 morbidly obese groups became normal; FPG and postprandial 2-hour glucose of IGT and DM group decreased to normal level; insulin level of 3 morbidly obese groups decreased obviously compared to pre-operation (all P<0.05), especially FINS and postprandial 2-hour insulin became normal without significant difference of control group (P>0.05), while postprandial 30-minute and 60-minute insulin levels in 3 groups were still higher as compared to control group. The insulin secretion curves of morbidly obese groups showed hyperinsulinemia before surgery. The peak of insulin secretion curve in IGT and DM group moved back to postprandial 120-minute before operation, and returned to 60-minute after operation, with basic normal rhythm of secretion curve. Preoperative HOMA-IR in all 3 morbidly obese groups was higher than that in control group (all P<0.05) and remarkably lower at postoperative 6-month compared to pre-operation(P<0.05). In 3 morbidly obese groups after operation, TG decreased, HDL-C increased, UA and TNF-α decreased significantly compared to before operation (all P<0.05). At postoperative 6-month, the HOMA-IR of DM group was positively correlated with BMI (r=0.236, P=0.004) and TNF-α (r=0.228, P=0.033), and was not correlated with HDL-C(P>0.05).</p><p><b>CONCLUSIONS</b>LSG can effectively ameliorate hyperinsulinemia and insulin secretion curve, and improve metabolic disorder and insulin resistance of different stage in obesity patients with glucose metabolic disorder. Insulin resistance is correlated with body weight and inflammatory factors.</p>

Study on the mechanisms of the variation of sexual hormone in young male obesity with acanthosis nigricans / 中华内分泌代谢杂志

Objective To assess the variation of sexual hormone and mechanisms of low testosterone in young male obesity with acanthosis nigricans. Methods Retrospective analysis was performed in 125 male obesity patients [ body mass index( BMI)≥28 kg/m2 ] . According to their clinical characteristics, they were divided into two groups including obesity without acanthosis nigricans(OB group, n=62) and obesity with acanthosis nigricans(AN group, n=63). 60 normal weight men were also recruited as a control group. Body fat and body weight were measured. Blood insulin, lipid profile, sex hormones levels, and inflammation factors were measured. Parameters of each group were compared and the correlations between total testosterone level and other index were analyzed. Results All the male obesities have the significant lower total testosterone levels than those of control group(P>0. 05), and those in AN group were lower than those in OB group(P>0. 05). The BMI and body fat in OB group and AN group were both significantly higher than those in control group(P>0. 05). The fasting insulin levels in all obese men were significantly higher than those in control group(P>0. 05), highest in AN group. Triglycerides(TG) in both OB and AN group were higher than those in controls, and not significant between later 2 groups. But high-density lipoprotein-cholesterol ( HDL-C) in the two groups were significantly lower than control, which in AN group were significantly lower than OB group. Total testosterone levels in AN group were negatively correlated with weight, waist circumference, hip circumference, fasting insulin, and homeostasis model assessment for insulin resistance ( HOMA-IR ) , and also negatively correlated with inflammation factors including C-reactive protein ( CRP ) , erythrocyte sedimentation rate ( ESR) , tumor necrosis factor-α( TNF-α) , and uric acid. However, total testosterone levels in AN group were not correlated with lipid metabolism index. Conclusion Young male obesity with acanthosis are associated with secondary hypogonadism. Hyperinsulinemia, insulin resistance, and inflammatory factors are risk factors for the occurrence of this secondary male hypogonadism.

Effect of laparoscopic sleeve gastrectomy on sex hormone in male severe obesity / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of laparoscopic sleeve gastrectomy(LSG) on sex hormone in male patients with severe obesity.</p><p><b>METHODS</b>Retrospective analysis was performed in 31 male patient with severe obese [body mass index(BMI) ≥28 kg/m, obesity group] who underwent LSG in Shanghai Tenth People's Hospital of Tongji University from December 2012 to May 2016. The anthropometric parameters(weight, BMI, waist circumference, hip circumference, waist-hip ratio, body fat percentage), glucose metabolic indices [fasting plasma glucose(FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), homeostasis model assessment-insulin resistance index(HOMA-IR)], and sex hormone parameters [estradiol(E2), total testosterone (TT), follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were collected preoperatively and 1, 3, 6 months postoperatively. In addition, 31 healthy male volunteers with normal BMI were consecutively recruited in this study as control group. The above-mentioned parameters were also determined in control group. Changes of these variables before and after surgery were analyzed. Pearson method was used to analyze the correlation of TT with anthropometric parameters and glucose metabolic indices before and after surgery.</p><p><b>RESULTS</b>The average age of patients in obesity and control group was (32.9±9.7) (18 to 56) years and (30.7±8.9) (18 to 49) years. Compared to the control group, obesity group had significantly higher anthropometric parameters and glucose metabolic indices before surgery (all P<0.05). In obesity group, the anthropometric and glucose metabolic indices significantly decreased at 1 to 6 months after surgery compared to those before surgery (all P<0.05). At 1 month after surgery, the anthropometric parameters and glucose metabolic indices in obesity group were significantly higher than those in control group (all P<0.05). At 3, and 6 months after surgery, there were no significant differences in glucose metabolic indices between obesity and control group (all P>0.05), while the anthropometric parameters in obesity group were still significantly higher than those in control group(all P<0.05). The sex hormone parameters in control and obesity group before surgery were as follows: E2: (100.2±23.5) pmol/L and (129.2±81.9) pmol/L; TT: (18.0±4.9) nmol/L and (8.4±4.5) nmol/L; FSH: (4.5±3.1) IU/L and (4.3±2.5) IU/L; LH: (4.4±1.7) IU/L and (5.3±2.6) IU/L. Compared to control group, the TT level of obese patients before surgery significantly decreased(P=0.000), while no significant differences were observed in the levels of E2, FSH, and LH(all P>0.05). The TT levels were significantly increased at 1, 3, 6 months after surgery[(13.1±7.0), (13.6±5.7), (21.0±19.3) nmol/L, respectively, all P<0.05] and the E2 level was significantly decreased at 6 months after surgery [(91.4±44.9) pmol/L, P<0.05], while no significant differences were observed at 1 and 3 months after surgery (all P>0.05). Furthermore, the FSH and LH levels did not exhibit significant change at 1, 3, and 6 months after surgery compared to those before surgery (all P>0.05). At 1 month after surgery, no significant correlations were examined in the change value of TT levels (▹TT) with the changes of BMI(▹BMI), FPG(▹FPG), FINS(▹FINS), HOMA-IR(▹HOMA-IR), and E2(▹E2) (all P>0.05). At 3 months after surgery, ▹TT was negatively correlated with ▹BMI (r=-0.441, P=0.015), ▹FINS (r=-0.375, P=0.041), and ▹HOMA-IR(r=-0.397, P=0.030), but not correlated with ▹FPG and ▹E2 (all P>0.05). At 6 months after surgery, ▹TT was negatively correlated with ▹BMI(r=-0.510, P=0.018) and ▹HOMA-IR (r=-0.435, P=0.049), but not correlated with ▹FPG, ▹FINS and ▹E2 (all P>0.05).</p><p><b>CONCLUSIONS</b>Male severe obese patients are accompanied with abnormal sex hormone levels. LSG has a significant effect on weight loss and blood glucose improvement, and may ameliorate the sex hormone unbalance by improving the insulin resistance in men with severe obesity.</p>