Objective:To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults.Methods:Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method.Results:Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P<0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc. BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the β values (95% CIs) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the β values (95% CIs) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions:BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14.

Objective:To investigate methods of molecular diagnosis and clinical features of 46, XY disorders of sexual development(DSD).Methods:A total of 206 cases of 46, XY DSD patients, who visited the Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine, from July 2009 to June 2021, underwent AA chip based on multiplex PCR and probe-capture-targeted next-generation sequencing. Clinical features of patients with genetic diagnosis were analyzed.Results:Among 206 patients, the diagnostic rate of patients with micropenis, hypospadias and cryptorchidism was the highest, up to 75.28%. Almost all patients had different degrees of undermasculinized external genitalia. The most frequent phenotype was micropenis with hypospadias(87.25%). Only one gene variant was detected in 81 patients(39.32%), multiple genetic variants were detected in 104 patients(50.49%), and no gene variant was identified in 21 patients(10.19%). 107 patients had definite genetic diagnosis, with a diagnostic rate of 51.94% by adding the pathogenic and likely pathogenic ratios following the American College of Medical Genetics and Genomics(ACMG) guidelines, including 40 patients of steroid 5α-reductase type 2(SRD5A2) variants(37.38%), 36 patients of androgen receptor(AR) variants(33.64%), 13 patients of steroidogenic factor 1(NR5A1) variants(16.82%), 6 patients of 17β-hydroxysteroid dehydrogenases 3(HSD17B3) variants(5.61%), 2 patients of 17α-hydroxylase/17, 20-lyase enzyme(CYP17A1), Wilms′ tumor 1(WT1) and GATA binding protein 4(GATA4) variants(1.87%), and one patient of luteinizing hormone receptor(LHCGR) variant(0.93%). Gynecomastia was found in 29 of 81 postpubertal patients, of which 25(86.21%) had AR variants.Conclusions:46, XY DSD presents complex clinical manifestations and molecular etiologies. Targeted nextgeneration sequencing has the advantages of high throughput, high efficiency and low cost, which has a high value especially in etiological diagnosis of 46, XY DSD with large genetic heterogeneity.

[Summary] The activities of 17α-hydroxylase and 17,20 lyase of cytochrome P450c17 were evaluated by ELISA in NCI-H295R cells after treatment with palmitate and oleate. The results showed that 0. 75 mmol/L plamitate did not influence the activity of 17α-hydroxylase, but increased the activity of 17, 20 lyase by 74. 3% ( P<0. 05). Oleate at the same concentration did not change the activity of 17,20 lyase. There were no significant changes in the protein expressions of P450c17, P450 oxidoreductase, and cytochrome b5 after treatment with palmitate and oleate. However,reactive oxygen species in cells were elevated by palmitate. The results suggest that exposure to palmitate may increase androgen production by inducing 17, 20 lyase activity of P450c17 in NCI-H295R cells, which is related with oxidative stress-mediated post-translational regulation of the enzyme.

Obj ectiev The purpose of this study is to assess the impact of bone metastasis on survival in non-small cell lung cancer(NSCLC),Which were treated with gefitinib for more than 6 months,and to identify the prognostic factors of patients with NSCLC presenting bone metastasis .Methods We compared the overall survival(OS), progression-free survival(PFS),1-year2,-year and 3-year survival rates between two cohorts based on bone metastasis ,as well as the prognostic factors in the patients with bone metastasis .Results In total, 76 patients were included in the study ,in which there are44 patients with no bone metastasis and32 patients with bone metastasis.The cohorts were similar in OS (19.000 ±3.317 months vs.26.000 ±2.121 months,P =0.625)as well as PFS (14.000 ±1.843 months vs.16.000 ±1.411 months,P=0.328).The 1-year survival rate was 63.6%in no bone metastasis cohort,but was increased to 96.9%in the other cohort.The survival rates at 2 years(34.1%vs.56.3%,P=0.054)and 3 years(18.2%vs.18.4%,P=0.950)were similar.The univa-riate analysis showed that a worse prognosis was more likely existed in elderly patients ( aged >60 years) and with pulmonary progression ,whereby factors including gender ,pathology s,moking index ,brain metastases ,bone related events and the application of radiotherapy ,bisphosphonates might not be independently associated with the surviv -al late.Analysis of multiple variables indicated a favorable prognosis for patients with no pulmonary progression . Conclusion This retrospective study shows that bone metastasis may not shorten the survival in patients whose pulmonary lesion was controlled by gefitinib .On the contrary ,pulmonary progression may be more likely the cause of death in patients with bone metastasis .Non suggestion is given to discontinue gefitinib when the bone metastasis appears.

ObjectiveThis paper reported our experience with thoracoscopic management of isolated atrial fibrillation to define the efficacy and safety of this approach.MethodsThirtytwo patients ( 17 mem,15 women) with isolated atrial fibrillation underwent thoracoscopic surgery.All procedures were finished under 3 port incisions on left posterior chest.Among them 18 cases are paroxysmal and 8 persistent.ResultsThere was no operative death or major perioperative complications.One case was converted to limited thoracotomy because of bleeding.Operation time was 87 - 238 min.Paroxysmal atrial fibrillation occurred in 9 cases in hospital and all the cases were sinus rhythm after discharge.Followup 4 to 20 months,One persistent case was converted paroxysmal.ConclusionPatients with isolated atrial fibrillation can benefited by Videoassisted thoracoscopic left posterior approach with better exposure of left atrial and resection of the left atrial appendage,with decreased operative trauma and better results.

ObjectiveTo summarize the clinical results of totally thoracoscopic cardiac surgery for mitral valve diseases.MethodsFrom May 2004 to October 2011,272 patients underwent totally thoracoscopic cardiac surgery for mitral valve diseases through three ports.Summarize the indication and contraindication are used and for the operation date.Results There was 1 case in-hospital deaths.The time of operations was 2.1 ～ 3.9 (3.0 ± 1.2 ) h.Time of cardiopulmonary bypass and aortic cross-clamp was 76 ～ 158 (98 ± 22) minites and 38 ～ 78 (52 ± 13 ) minites.Time of mechanical ventilation and intensive care unit stay was 5.8 ～ 34.5 ( 11.2 ± 3.6 ) hours and 14 ～ 67 ( 28.2 ± 7.6 ) hours.The volume of drainage was 20 ～ 1200(370 ± 80) ml.The hospital days were 7 ～ 18 ( 10.2 ± 2.1 ) days.The postoperative complications occurred in 14 cases.ConclusionTotally thoracoscopic cardiac surgery for mitral valve diseases is technically feasible and safe with less drainage and shortened hospital stay.

Objective To investigate the episodic memory monitoring ability in patients with Parkinson' s disease (PD) and explore the mechanism of the episodic memory impairment.Method The feeling-of-knowing (FOK) paradigm were established and subsequently administered in 25 PD patients and 25 healthy control (HC) participants who were matched in age and educational level.Results Compared with healthy control group ( FOK-EM recall 39.67％ ±6.11％ ; recognition 58.42％ ±7.50％ ; FOK accuracy 0.61 ±0.22),the episodic memory and its monitoring ability in PD patients were significantly impaired on the accuracy rate of FOK-EM recall ( 19.33％ ±5.10％,t =-4.833,P ＜0.01 ),recognition (45.93％ ±7.82％,t =-2.497,P ＜0.05) and FOK accuracy( -0.18 ±0.46,t =-5.986,P ＜0.01).Furthermore,the correct judgment and correct recognition of FOK-EM ( 20.47％ ± 10.78％ ) and the correct judgment and false recognition of FOK-EM (29.53％ ±5.62％ ) in the PD group were significantly higher than the HC group ( the correct judgment and correct recognition of FOK-EM:39.47％ ± 9.47％ and the correct judgment and false recognition of FOK-EM:13.90％ ±5.50％ ; t =3.564,P ＜0.05 ; t =2.306,P ＜0.05).Most importantly,the stroop effect was positively correlated with the correct judgment and false recognition of FOK-EM in PD group ( r =0.640,P ＜ 0.05 ).Conclusions In the present study,the PD patients demonstrated an overestimation of their recognition ability of episodic memory,moreover,this impairment of memory monitoring was positively correlated with the deficit of executive function,indicating that this mechanism could be an influential factor of memory disorder in PD.

ObjectiveTo investigate the event-based prospective memory (EBPM) and time-based prospective memory (TBPM) in patients with Alzheimer' s disease (AD). MethodsTwenty patients with AD, 20 adults with amnesia mild cognitive impairment (aMCI) and 30 healthy adults with matched age and education level were assessed with a battery of neuropsychological tests including EBPM and TBPM tasks.ResultsCompared with healthy elders and patients with aMCI on performance of PM (2. 23 + 0. 77,4.83 ±1.09;1.00±1.03,3. 10 ± 1.52) and episodic memory(0. 70 ±0. 12,0.66 +0. 16;0.45 ±0.07,0.54±0. 10), AD patients were all impaired in PM and episodic memory(0.20 +0.41,2.05 ± 1.43;0.33±0. 12,0.32±0. 10), and were impaired in EBPM more significantly (t=-2.792, P＜0.01;t =-10. 761 ,P ＜0. 01 ). ConclusionsThese results suggest that AD patients show deficits of PM, but their EBPM is impaired more significantly. EBPM impairment may be an early diagnostic of AD.

Objective To explore the impairment of time perception in patients with Parkinson's disease (PD).Method Thirty-two individuals with idiopathic PD were compared with 32 matched healthy controls using a time reproduction task.Result Compared with healthy controls for the 3-second duration reproduction task, PD patients in the setting of a delay by 1 s ( (2.78 ±0.31 ) s and (2.15 ±0.34) s,respectively) and a delay by 5 s ( (2.74 ±0.32) s and (2.08 ±0.37) s, respectively) showed impairment in time perception with a significant under-estimation of the duration ( t = - 7.459, - 7.533, both P ＜0.01 ).When compared with healthy controls for the 5-second duration reproduction task, PD patients in the setting of a delay by 1 s ( (3.99 ±0.39) s and (3.11 ±0.52) s) and 5 s ( (4.05 ±0.40) s and (2.96 ±0.54) s) also showed impairment in time perception with a significant under-estimation of the duration (t =-7.609 and - 9.120, both P ＜ 0.01 ).When compared with healthy controls for the 600-millisecond duration reproduction task, PD patients in the setting of delay by 1 s ((0.91 ±0.18) s and (0.90 ±0.18) s, respectively) and by 5 s ( (0.89 ± 0.16) s and (0.91 ± 0.17 ) s, respectively) did not have impaired time perception, and the difference was not significant ( t = 0.347, P = 0.730; t = - 0.519, P =0.606, respectively).Conclusion Our data indicates that time perception is impaired in PD patients.Impaired time perception is mainly an under-estimation of the time interval in seconds rather than milliseconds.

Objective To investigate the characteristics of memory impairment in patients with amnestic mild cognitive impairment (aMCI). Methods Thirty-five patients with aMCI and 35 healthy adults matched with age and education level were administered with a neuropsychological battery of tests including conception and perception implicit priming tasks (category exemplar, picture identification), as well as explicit memory tasks (immediate recall, delay recall, delay recognition ). Results Compared with healthy elders, patients with aMCI were impaired in the conception implicit priming task(t=-4.33, P<0.01), as well as in explicit memory (immediate recall, t=6.40, P<0.01;delay recall, t=9.29,P<0.01; delay recognition, t=7.65,P<0.01),but not in perception implicit priming task (t=-0.78, P＞0.05).The conception implicit priming is positively correlated with verbal fluency (r=0.74,P<0.01). Conclusions The present results indicate that patients with aMCI are impaired in both explicit memory and conception implicit priming. The conception implicit priming impairment in aMCI may be related to their frontal lobe dysfunction.