Background:The diversity and function of gut microbiota have been regarded as crucial factors affecting human health.With the advances in genetics and epidemiology,especially the application of Mendelian randomization analysis,a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer.Aims:To investigate the causal relationship between gut microbiota and duodenal ulcer through two-sample Mendelian randomization analysis.Methods:Genetic variation samples of the gut microbiota were screened from the MiBioGen database.Genetic loci related to duodenal ulcer were selected as instrumental variables from genome-wide association study.The inverse-variance weighted method,weighted median method,and MR-Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer.Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results.Results:Bacteroides(OR=0.998,95%CI:0.996-1.000,P=0.014),Prevotella_7(OR=0.999,95%CI:0.998-1.000,P=0.043)and Terrisporobacter(OR=0.998,95%CI:0.997-1.000,P=0.029)exhibited negative causal relationship with duodenal ulcer,while Bifidobacterium(OR=1.001,95%CI:1.000-1.003,P=0.046),Lachnoclostridium(OR=1.002,95%CI:1.001-1.004,P=0.007)and Olsenella(OR=1.001,95%CI:1.000-1.002,P=0.018)presented positive causal relationship with duodenal ulcer.The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded.Conclusions:The two-sample Mendelian randomization analysis revealed that Bacteroides,Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer,while Bifidobacterium,Lachnoclostridium and Olsenella were risk factors.

Background:The diversity and function of gut microbiota have been regarded as crucial factors affecting human health.With the advances in genetics and epidemiology,especially the application of Mendelian randomization analysis,a novel perspective has been provided for profoundly uncovering the causal relationship between gut microbiota and duodenal ulcer.Aims:To investigate the causal relationship between gut microbiota and duodenal ulcer through two-sample Mendelian randomization analysis.Methods:Genetic variation samples of the gut microbiota were screened from the MiBioGen database.Genetic loci related to duodenal ulcer were selected as instrumental variables from genome-wide association study.The inverse-variance weighted method,weighted median method,and MR-Egger regression analysis were used to assess the causal relationship between gut microbiota and duodenal ulcer.Tests for heterogeneity and horizontal pleiotropy were conducted to ensure the stability of the results.Results:Bacteroides(OR=0.998,95%CI:0.996-1.000,P=0.014),Prevotella_7(OR=0.999,95%CI:0.998-1.000,P=0.043)and Terrisporobacter(OR=0.998,95%CI:0.997-1.000,P=0.029)exhibited negative causal relationship with duodenal ulcer,while Bifidobacterium(OR=1.001,95%CI:1.000-1.003,P=0.046),Lachnoclostridium(OR=1.002,95%CI:1.001-1.004,P=0.007)and Olsenella(OR=1.001,95%CI:1.000-1.002,P=0.018)presented positive causal relationship with duodenal ulcer.The sensitivity analysis indicated that the influences of heterogeneity and horizontal pleiotropy on the causal relationship could be excluded.Conclusions:The two-sample Mendelian randomization analysis revealed that Bacteroides,Prevotella_7 and Terrisporobacter were protective factors for duodenal ulcer,while Bifidobacterium,Lachnoclostridium and Olsenella were risk factors.

Objective:To investigate the effect of LRRK2G2019S mutation on activation of microglia after iron deprivation and its mechanism.Methods:(1) Microglia were differentiated from human induced pluripotent stem cells (IPSC) with the help of hematopoietic progenitor cells (HPC) and identified by immunofluorescent staining, and α-synuclein (α-syn) A53T mutant protein was obtained by protein purification technology. (2) Microglia were divided into control group, α-syn group, α-syn+ deferoxamine (DFO) group; phosphate buffer solution (PBS), 1 μmol/L purified α-syn A53T mutant protein, 1 μmol/L purified α-syn A53T mutant protein+30 mmol/L DFO were given respectively for 24 h. Fe 2+ concentration was detected by colorimetry, Rab35 protein expression was detected by Western blotting, intracellular reactive oxygen species (ROS) level was detected by flow cytometry, and interleukin-6 ( IL-6), tumor necrosis factor-α ( TNF-α) and transforming growth factor-β ( TGF-β) mRNA expressions were detected by real time-PCR (RT-PCR); microglia culture supernatant (MCS) in the 3 groups were transfered to SH-SY5Y cells, and SH-SY5Y cell apoptosis was detected by flow cytometry. (3) Bidirectional DNA sequencing was used to detect leucine rich repeat kinase 2 ( LRRK2) gene mutations in microglia treated with 1 μmol/L purified α-syn A53T mutant protein. Microglia were divided into control group, α-syn group and α-syn+GSK3357679A group, and treated with corresponding drugs for 24 h, respectively (LRRK2 inhibitor GSK3357679A concentration: 10 nmol/L), and LRRK2 protein expression was detected by Western blotting; microglia were divided into control group, α-syn group, α-syn+GSK3357679A, and α-syn+GSK3357679A+DFO group, and treated with corresponding drugs for 24 h, Rab35 protein expression was detected by Western blotting, intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (4) Microglia were divided into control group, α-syn group, α-syn+rapamycin (RAPA) group, and treated with corresponding drugs for 24 h (concentration of autophagy inducer RAPA: 50 nmol/L); protein expressions of Rab35, P62 and microtubule-associated protein light chain 3 II (LC3II) were detected by Western blotting; intracellular ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. (5) Microglia were divided into control group, α-syn group, and α-syn+Rab35 group, and treated with corresponding drugs for 24 h (concentration of Rab35 overexpressed plasmids: 1 μg/mL); Rab35, P62, and LC3II protein expressions were detected by Western blotting; ROS level was detected by flow cytometry, and IL-6, TNF-α and TGF-β mRNA expressions were detected by RT-PCR. Results:(1) Immunofluorescent staining showed negative neuronal nuclei (NeuN) expression and positive ionized calcium-binding adapter molecule 1 (Iba1) expression in microglia, and high LRRK2 expression; PcDNA3.1-SNCA-A53T expression plasmid was constructed and α-syn A53T mutant protein was purified. (2) The Fe 2+ concentration in α-syn group was significantly higher than that in control group, and the Fe 2+ concentration in α-syn+DFO group was significantly lower than that in α-syn group ( P<0.05); the Rab35 protein and TGF-β mRNA expressions in control group, α-syn group and α-syn+DFO group were decreased successively, while the IL-6 and TNF-α mRNA expressions were increased successively, with significant differences ( P<0.05); ROS level and SH-SY5Y cell apoptosis rate in control group, α-syn group, α-syn+DFO group were increased successively. (3) Bidirectional DNA sequencing showed that the LRRK2G2019S mutation in microglia was the most obvious after α-syn A53T mutant protein stimulation; compared with the control group, the α-syn group had significantly increased LRRK2 protein expression, while the α-syn+GSK3357679A group had significantly decreased LRRK2 protein expression compared with α-syn group ( P<0.05); compared with the control group, the α-syn group had significantly decreased Rab35 protein and TGF-β mRNA expressions, and statistically increased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+GSK3357679A group had significantly increased Rab35 protein and TGF-β mRNA expressions, and statistically decreased IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn+GSK3357679A group, α-syn+GSK3357679A+DFO group had significantly increased IL-6 and TNF-α mRNA expressions, and significantly decreased Rab35 protein and TGF-β mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group, the α-syn+GSK3357679A group had lower ROS level than the α-syn group, and the α-syn+GSK3357679A+DFO group had higher ROS level than the α-syn+GSK3357679A group. (4) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly increased P62 protein, IL-6 and TNF-α mRNA expressions ( P<0.05); compared with α-syn group, the α-syn+RAPA group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); the α-syn group had higher ROS level than the control group and α-syn+RAPA group. (5) Compared with the control group, the α-syn group had significantly decreased Rab35 and LC3II protein, and TGF-β mRNA expressions, and statistically increased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05); compared with the α-syn group, the α-syn+Rab35 group had significantly increased Rab35 and LC3II protein, and TGF-β mRNA expressions, and significantly decreased P62 protein, and IL-6 and TNF-α mRNA expressions ( P<0.05). The α-syn group had higher ROS level than the control group and α-syn+Rab35 group. Conclusion:LRRK2G2019S can induce neuroinflammation by inhibiting Rab35-related autophagy under iron deprivation, and Rab35 is expected to be a key factor in intervening neuroinflammation.

Mixed lineage kinase domain-like protein (MLKL) is a pseudokinase with a kinase domain, which plays an important role in the regulation of necroptosis. After cerebral ischemia, MLKL, as the substrate protein of the receptor-interacting protein 3, undergoes oligomerization and phosphorylation, and then translocates from the cytoplasm to the plasmalemma, causing mitochondrial division and cell membrane rupture. MLKL can also mediate the inflammatory response after cerebral ischemia by inducing necroptosis and directly activating inflammasomes, thereby aggravating brain injury. Therefore, to clarify the biological characteristics of MLKL and its role and mechanism in cerebral ischemia is very important for the treatment of cerebral ischemia.

Objective:To investigate the contraceptive status and influencing factors of women at reproductive age of chronic kidney disease (CKD), so as to provide evidence for improving reproductive health of women with CKD.Methods:A total of 256 female patients of reproductive age of CKD from November 2017 to February 2019 at National Clinical Research Center of Kidney Diseases, Jinling Hospital were selected to investigate the contraceptive status. And the investigation results were analyzed.Results:A total of 256 patients were investigated, and 246 valid question-naires were collected. Eighty-nine (36.18%) patients did not use contraceptive methods, 131 (53.25%) patients used one contraceptive method, and 26 (10.57%) patients used two or more contraceptive methods. The proportion of contraceptive users in order were condoms 51.59%, intrauterine devices 45.86%, oral drugs 7.01%, safe period 7.01%, external ejaculation 5.10%, and contraceptive injection 0.64%. Univariate analysis showed that age, marital status, one-child status, birth status, partner's attitude towards contraception, whether to accept contraceptive guidance, whether to have edema, and the number of children they intended to have were all related to the use of contraceptive measures, with statistically significant differences ( P<0.05). Multivariate regression analysis showed that those who were married, had 2 or more children, received contraceptive guidance, and had a positive attitude towards contraception were more likely to take contraceptive measures ( P<0.05). Conclusion:Child-bearing age women with CKD have a lower rate of contracep-tive use, especially long-duration contraception, and a higher risk of unintended pregnancy. Nurses should strengthen the propaganda and education of contraceptive knowledge of CKD patients, and take targeted intervention measures to improve the utilization rate of contraceptive tools.

Objective:To investigate the contraceptive status and influencing factors of women at reproductive age of chronic kidney disease (CKD), so as to provide evidence for improving reproductive health of women with CKD.Methods:A total of 256 female patients of reproductive age of CKD from November 2017 to February 2019 at National Clinical Research Center of Kidney Diseases, Jinling Hospital were selected to investigate the contraceptive status. And the investigation results were analyzed.Results:A total of 256 patients were investigated, and 246 valid question-naires were collected. Eighty-nine (36.18%) patients did not use contraceptive methods, 131 (53.25%) patients used one contraceptive method, and 26 (10.57%) patients used two or more contraceptive methods. The proportion of contraceptive users in order were condoms 51.59%, intrauterine devices 45.86%, oral drugs 7.01%, safe period 7.01%, external ejaculation 5.10%, and contraceptive injection 0.64%. Univariate analysis showed that age, marital status, one-child status, birth status, partner's attitude towards contraception, whether to accept contraceptive guidance, whether to have edema, and the number of children they intended to have were all related to the use of contraceptive measures, with statistically significant differences ( P<0.05). Multivariate regression analysis showed that those who were married, had 2 or more children, received contraceptive guidance, and had a positive attitude towards contraception were more likely to take contraceptive measures ( P<0.05). Conclusion:Child-bearing age women with CKD have a lower rate of contracep-tive use, especially long-duration contraception, and a higher risk of unintended pregnancy. Nurses should strengthen the propaganda and education of contraceptive knowledge of CKD patients, and take targeted intervention measures to improve the utilization rate of contraceptive tools.

Objective To investigate the feasibility of urethral prefabrication with vaginal mucosa in female-to-male transsexuals and to compare the urologic complications after penile reconstruction in female-to-male transsexuals between prefabrication group and forearm group.Methods Prefabrication of the neourethra with tubed vaginal mucosal graft was performed for 22 female-to-male transsexual patients from 2007 to 2016,while radial forearm flap,known as the traditional tube-within-tube method,was used to construct the neourethra for other 31 cases.Results All of the reconstructed penises survived completely and allowed the patients to urinate while standing in the prefabrication group.Phalloplasty by using the vaginal mucosal graft for urethroplasty significantly decreased the donor scar,the duration of the second operation and the incidence rates of urologic strictures,comparing with the forearm group (P＜0.05).Conclusions It is reliable to use the prefabrication of the neourethra with tubed vaginal mucosal graft in phalloplasty female-to-male transsexual patients.