Oyecave:To observe the influence of nociceptin/orphanin FQ(N/OFO)on cerebral infarction volume and somatosellsOry evoked potential(SEP)in focal cerebral ischemia in rats.Methods:Forty one SD rats were randomly alloomed into middle artery occlusion(MCAO)sham-operation(n=5),isehemic(n=8),N/OFQ 10μg(n=7),N/OFQ 1 μg(n=7),N/OFQ0.1 μg(n=7),and artificiai cerebrospinal fluid(ACSF)(n=7)groups.A model of middle cerebral artery occlusion(MCAO)in rats was induced using intraluminal suture method.Reperfusion was performed 2 hours after MCAO.One hour after MCAO,N/OFQ 10 μg,N/OFQ 1 μg,N/OFQ O. 1 μg,and the same volume of ACSF were injected intraventricularly in the N/OFQ 10 μg,N/OFQ 1 μg,N/OFQ 0. 1 μg,and ACSF groups,respectively. The cerebral infarction volurne was detected 24 hours after reperfusion,and SEP was recorded. Results:1he amplitude of SEP P1 decreased in the sham-operation group. There was no significant change in P1 peak latencies.There were no significant differences hetween the N/OFQ 0. 1 μg group and the ACSF group in SEP amplitudes,P1 peak lantecies and cerebral infarction volume. As compared with the ACSF group,the SEP amplitudes were further decreased in the N/OFQ 1 μg and N/OFQ 10 μg groups,but there were no significant change in P1 peak lantecies. One hour after reperfusion,the SEP amplitude in the ACSF group almost returned to the level of preischemia,the recovery slowed down in the N/OFQ 1 μg group,and it still did not recovered 3 hours after reperfusion in the N/OFQ 10 μg group. The dose of N/OFQ and SEP response showed dose-effect relationship,The higher the dose,the deeper the SEP depression and the slower the recovery. At 24 hours after reperfusion,the cerebral infarction vlumes in the shamoperation,ACSF,N/OFQ 0. 1 μg,N/OFQ 1 μg,and N/OFQ 10 μg groups were 0 mm3,24.180 ±4.088 mm3,23.090±4.523 mm3,35.304 ± 6. 824 mm3,and 40. 806±6. 716 mm3,respectively. There was no significant difference between N/OFQ 0. 1 and ACSF groups. There were significant differences between N/OFQ 1 μg and 10 μg groups and ACSF group (all P ＜ 0.01 ). Conclusions:Intracerebroventricular injection of N/OFQ in the early stage of cerebral ischemia decreases the SEP amplitude,prolongs the time of recovery,and increases cerebral infarction volume,which shoves that it may aggravate cerebral ischemic injury.

ObjectiveTo investigate the effect of intensive insulin therapy in critically ill elderly patients.MethodsElderly patients ( ≥ 65 years) admitted to the ICU of Beijing Tongren Hospital from June 2005 to December 2007 were divided into Group A ( glucose control target was 4.4-6.1mmol/L) and Group B ( glucose control target was 7.3-8.3mmol/L).Blood glucose level was controlled with a computer-assisted glucose control protocoL ResultsA total of 639 patients were enrolled,of which 280 were in Group A and 359 in Group B.The mean blood glucose level of the 2 groups was (6.07 ± 0.56) mmol/L and (7.52 ± 0.87 ) mmol/L respectively,both within the target ranges.The hyperglycemic index was (0.69±0.44) mmol/L in Group A and ( 1.60 ±0.73) mmol/L in Group B (P =0.000).No hypoglycemia adverse events occurred in either group.No significant differences were observed in the length of stay in ICU,duration of mechanical ventilation,hospitalization expenses,ICU mortality,and hospital mortality of the 2 groups.ConclusionMaintaining the blood glucose level of critically ill elderly patients at ≤8.3 mmol/L is safe and practical.

Objective To investigate the long-term outcome of radical prostatectomy (RP) in the patients with incidental prostate cancer (IPCa) detected by surgery of benign prostatic hyperplasia (BPH) and to evaluate the risk factors for residual tumour after BPH surgery and biochemical recurrence in patients with IPCa treated with RP.Methods We retrospectively analyzed the clinical and follow-up data of 45 patients with IPCa detected by surgery of BPH and undergoing RP from January 2004 to October 2016.The age,PSA before and after BPH surgery,prostate volume,T stage and Gleason score after the BPH surgery,T stage at RP (pT0,pT2,pT3),Gleason score at RP and status of biochemical recurrence were recorded.Multivariate logistic regression analysis addressed the association between the factors and the presence of residual cancer after the surgery for BPH.Cox regression was used to analyzed the relationship between the factors and the rate of biochemical recurrence after RP.Results Among 45 IPCa patients,21 patients were stage T1a and 24 were stage T1b.After RP,7 (15.6％) patients had no residual tumor (pT0).PSA before BPH surgery (RR =2.58,95％ CI 1.27-5.42,P =0.04),PSA after BPH surgery (RR =4.26,95％ CI 2.57-7.64,P =0.01) and Gleason score after BPH surgery (RR =3.98,95％ CI 1.85-5.77,P =0.02) were significant associated factors with the residual cancer after BPH surgery.With a mean follow-up of 54 months(ranging 5-144 months),the 5-and 10-years.biochemical recurrence-free survival rates were 95.6％ and 86.7％,respectively.PSA after surgery for BPH (RR =4.79,95％ CI 2.57-7.64,P =0.02) and Gleason score after RP(RR =2.01,95％ CI 1.74-5.21,P =0.04) were the only independent risk factors for biochemical recurrence.Stage (T1a-T1b) did not predict residual cancer or the rate of biochemical recurrence (P ＞ 0.05).Conclusions RP in the patients with IPCa detected by BPH surgery had a good outcome of long-term oncological control.PSA before and after BPH surgery and Gleason score at BPH surgery were the significant associated factors of residual cancer after BPH surgery.PSA after BPH surgery and Gleason score at RP were the only independent risk factors for biochemical recurrence.

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.

Objective: To investigate the methods and short-time clinical results of reconstruction of Paprosky type Ⅲ acetabulum bone defects by using tantalum augments. Methods: A total of 17 patients (17 hips) with Paprosky type Ⅲ acetabulum bone defects, treated with tantalum augments in revision of total hip arthroplasty at Department of Orthopedics Surgery in General Hospital of Chinese People′s Liberation Army were retrospectively analyzed from March 2014 to May 2016.There were 6 males and 11 females aged from 23 to 74 years with an average of (50.2±16.3) years. Tantalum augments or TM-Cup augment (the cup-on-cup technique) were used to reconstruct the defects.The TM-Cup augment was the tantalum revision cup which was removed titanium ring. The cup-on-cup technique combined TM-Cup augment and biological acetabulum cup. Augments were served as the nonresorptive structural allograft in revision of total hip arthroplasty. Harris hip score was used to evaluate clinical effects. The vertical position of the rotation center was measured and analyzed. Radiographic assessments of the acetabular components were performed by DeLee-Charnley and the Anderson criteria and recorded postoperative complications. Results: All the patients were followed up from 3 to 29 months with an average of (16.2±5.4) months, tantalum augments and biological acetabulum cup were used in 13 patients, the TM-Cup augment and biological acetabulum cup were used in 4 patients. At the time of the latest follow-up, the mean Harris hip score increased compared to preoperatively (86.8±8.3 vs. 30.0±12.0) (t=12.78, P<0.01), the average vertical location of the center of rotation was decreased ((25.3±9.8) mm vs.(47.6±10.5)) mm (t=4.95, P<0.01). All the tantalum augments and biological acetabulum cups were stable, there were no infection, dislocation and other complications. Conclusions The use of tantalum augments could be considered as an effective management of Paprosky type Ⅲ defects providing good clinical and radiographic outcomes in the short term.The cup-on-cup technique which was used in reconstruction of severe superior-invagination acetabular bone defects and restoration relatively normal center of rotation had special application value.

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.

OBJECTIVETo assess the effects of laparoscopic sleeve gastrectomy (LSG) on insulin secretion mode and metabolism of glucose and lipid in morbidly obese patients.

METHODSClinical 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.

RESULTSBody 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).

CONCLUSIONSLSG 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.

OBJECTIVETo investigate the effect of laparoscopic sleeve gastrectomy(LSG) on sex hormone in male patients with severe obesity.

METHODSRetrospective 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.

RESULTSThe 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).

CONCLUSIONSMale 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.

Adult ; Bariatric Surgery ; Blood Glucose ; physiology ; Body Mass Index ; Body Weights and Measures ; China ; Estradiol ; blood ; physiology ; Fasting ; blood ; Follicle Stimulating Hormone ; blood ; physiology ; Follow-Up Studies ; Gastrectomy ; Glycated Hemoglobin A ; physiology ; Humans ; Insulin ; blood ; physiology ; Insulin Resistance ; physiology ; Luteinizing Hormone ; blood ; physiology ; Male ; Obesity, Morbid ; surgery ; Retrospective Studies ; Testosterone ; blood ; physiology ; Treatment Outcome ; Weight Loss ; physiology

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.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

INTRODUCTION: Observational studies have revealed an association between waist circumference (WC) and atrial fibrillation (AF). However, it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk factors. Therefore, the causal role of WC in AF is unclear. This study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization (MR) analysis. METHODS: In our two-sample MR analysis, the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study (GWAS) of WC (42 single nucleotide polymorphisms with a genetic significance of P <5 × 10 -8 ). The data of WC (from the Genetic Investigation of ANthropometric Traits consortium, containing 232,101 participants) and the data of AF (from the European Bioinformatics Institute database, containing 55,114 AF cases and 482,295 controls) were used to assess the causal role of WC on AF. Three different approaches (inverse variance weighted [IVW], MR-Egger, and weighted median regression) were used to ensure that our results more reliable. RESULTS: All three MR analyses provided evidence of a positive causal association between high WC and AF. High WC was suggested to increase the risk of AF based on the IVW method (odds ratio [OR] = 1.43, 95% confidence interval [CI], 1.30-1.58, P = 2.51 × 10 -13 ). The results of MR-Egger and weighted median regression exhibited similar trends (MR-Egger OR = 1.40 [95% CI, 1.08-1.81], P = 1.61 × 10 -2 ; weighted median OR = 1.39 [95% CI, 1.21-1.61], P = 1.62 × 10 -6 ). MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and AF. CONCLUSIONS Our findings suggest that greater WC is associated with an increased risk of AF. Taking measures to reduce WC may help prevent the occurrence of AF.
Humans ; Atrial Fibrillation/genetics* ; Genome-Wide Association Study ; Waist Circumference/genetics* ; Computational Biology ; Databases, Factual