Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Pulmonary hypertension is a rare and progressive illness with a devastating prognosis. Promising research efforts have advanced the understanding and recognition of the pathobiology of pulmonary hypertension. Despite remarkable achievements in terms of improving the survival rate, reducing disease progression, and enhancing quality of life, pulmonary arterial hypertension (PAH) is not completely curable. Therefore, an effective treatment strategy is still needed. Recently, many studies of the underlying molecular mechanisms and technological developments have led to new approaches and paradigms for PAH treatment. Management based on stem cells and related paracrine effects, epigenetic drugs and gene therapies has yielded prospective results for PAH treatment in preclinical research. Further trials are ongoing to optimize these important insights into clinical circumstances.

背景:保留十二指肠的胰头切除术是替代胰十二指肠切除术治疗良性肿瘤、囊性肿瘤及神经内分泌瘤的可行之选。方法:检索Pubmed、Embase及Cochrane数据库中保留十二指肠胰头切除术的研究结果。根据手术指征、围手术期并发症及微创应用等纳入1994年1月至2021年3月的38项队列研究共702例患者的临床资料。结果:共702例患者分别因良性肿瘤、癌前病变、囊性肿瘤、胰腺神经内分泌肿瘤、十二指肠乳头周围腺瘤等行保留十二指肠的胰头切除术。702例患者中，214例（30.5%）行保留十二指肠的部分胰头切除术，488例（69.5%）行保留十二指肠的全胰头切除术，后者中微创手术占17.3%。两种术式的术后早期严重并发症发生率（术后B及C级胰瘘、胆瘘、腹腔出血及腹腔脓肿）均<10%，围手术期病死率分别为0和1.02%。经中位时间为（50.7±21.1）个月的随访，局部复发率为2.8%（15/404）。结论:保留十二指肠的胰头切除术应作为胰头部分支胰管型导管内乳头状肿瘤、实性假乳头状肿瘤、黏液性囊腺瘤、>2 cm的有或无功能的良性内分泌肿瘤外科治疗的首选术式。

背景:保留十二指肠的胰头切除术是替代胰十二指肠切除术治疗良性肿瘤、囊性肿瘤及神经内分泌瘤的可行之选。方法:检索Pubmed、Embase及Cochrane数据库中保留十二指肠胰头切除术的研究结果。根据手术指征、围手术期并发症及微创应用等纳入1994年1月至2021年3月的38项队列研究共702例患者的临床资料。结果:共702例患者分别因良性肿瘤、癌前病变、囊性肿瘤、胰腺神经内分泌肿瘤、十二指肠乳头周围腺瘤等行保留十二指肠的胰头切除术。702例患者中，214例（30.5%）行保留十二指肠的部分胰头切除术，488例（69.5%）行保留十二指肠的全胰头切除术，后者中微创手术占17.3%。两种术式的术后早期严重并发症发生率（术后B及C级胰瘘、胆瘘、腹腔出血及腹腔脓肿）均<10%，围手术期病死率分别为0和1.02%。经中位时间为（50.7±21.1）个月的随访，局部复发率为2.8%（15/404）。结论:保留十二指肠的胰头切除术应作为胰头部分支胰管型导管内乳头状肿瘤、实性假乳头状肿瘤、黏液性囊腺瘤、>2 cm的有或无功能的良性内分泌肿瘤外科治疗的首选术式。

Concurrent involvement of bilateral renal and cerebral arteries, usually incurred as stenosis, is rare in childhood-onset Takayasu arteritis (c-TA). We report the case of a 14-year-old girl, with c-TA, presenting with transient ischemic attack after endovascular revascularization for renal artery stenosis and cerebrovascular stroke after surgical revascularization for cerebral artery stenosis associated with childhood-onset moyamoya syndrome. We deem that decrease of blood pressure by endovascular revascularization and improvement of cerebral perfusion by surgical revascularization may have jeopardized the cerebral deep watershed zone to cerebral ischemia followed by cerebral hyperperfusion syndrome and caused transient ischemic attack and cerebrovascular stroke in our patient. Revascularization could be a double-edge sword for c-TA patients presenting with concomitant renal artery stenosis and cerebral artery stenosis, and should be performed with caution. Quantitative analysis of cerebral blood flow by brain magnetic resonance imaging and angiography should be performed within 48 hours after surgical revascularization in c-TA.
Adolescent* ; Angiography ; Blood Pressure ; Brain ; Brain Ischemia ; Cerebral Arteries* ; Cerebrovascular Circulation ; Constriction, Pathologic* ; Female* ; Humans ; Hypertension, Renovascular ; Ischemic Attack, Transient ; Magnetic Resonance Imaging ; Moyamoya Disease* ; Perfusion ; Renal Artery Obstruction ; Stroke ; Takayasu Arteritis*

The aim of the present study was to investigate the effects of exercise on skeletal muscle autophagy. Trains of high-frequency electrical stimulation (pulses frequency: 100 Hz) were used to stimulate sciatic nerve and consequently induce muscle contraction of the left hindlimb. The unstimulated right hindlimb muscles were taken as control. The mice were sacrificed immediately (0), 30 or 60 min after the electrical stimulation by cervical dislocation, and gastrocnemius muscles were rapidly dissected and freeze-clamped in liquid nitrogen. AMP-activated protein kinase (AMPK) and the autophagy marker protein LC3 were detected by Western blotting, and muscle atrophy related genes including atrogin-1, MuRF-1, Bnip3, Bnip3l and CathepsinL were detected by using real-time qPCR. The results showed that, at 0 min after the electrical stimulation, the activity of AMPK and LC3-II/I ratio were significantly increased in left gastrocnemius muscles, compared with those of the muscles in the right hindlimb. The levels of atrogin-1, MuRF-1, Bnip3, Bnip3l and CathepsinL mRNA expressions were up-regulated by electrical stimulation. Meanwhile, the activity of autophagy related protein, ULK1 was significantly enhanced by electrical stimulation. These results suggest that electrical stimulation of sciatic nerve may induce the skeletal muscle autophagy, and this may be regulated through AMPK/ULK1-mediated signaling pathway.

Objectives. Polymorphisms in metabolic genes which alter rates of bioactivation and detoxification have been shown to modulate susceptibility to colorectal cancer. This study sought to evaluate the colorectal cancer risk from environmental factors and to do polymorphism studies on genes that code for Phase I and II xenobiotic metabolic enzymes among Filipino colorectal cancer patients and matched controls. Methods. A total of 224 colorectal cancer cases and 276 controls from the Filipino population were genotyped for selected polymorphisms in GSTM1, GSTP1, GSTT1, NAT1 and NAT2. Medical and diet histories, occupational exposure and demographic data were also collected for all subject participants.Results. Univariate logistic regression of non-genetic factors identified exposure to UV (sunlight) (OR 1.99, 95% CI: 1.16-3.39) and wood dust (OR 2.66, 95% CI: 1.21-5.83) and moldy food exposure (OR 1.61, 95% CI:1.11-2.35) as risk factors; while the NAT2*6B allele (recessive model OR 1.51, 95% CI :1.06-2.16; dominant model OR 1.87, 95% CI: 1.05-3.33) and homozygous genotype (OR 2.19, 95% CI: 1.19-4.03) were found to be significant among the genetic factors. After multivariate logistic regression of both environmental and genetic factors, only UV radiation exposure (OR 2.08, 95% CI: 1.21-3.58) and wood dust exposure (OR 2.08, 95% CI: 0.95-5.30) remained to be significantly associated with increasing colorectal cancer risk in the study population.Conclusion. This study demonstrated that UV sunlight and wood dust exposure play a greater role in influencing colorectal cancer susceptibility than genotype status from genetic polymorphisms of the GST and the NAT` genes.
Colorectal Neoplasms ; Polymorphism, Genetic