Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

ObjectiveOptimize the latex perfusion technique and apply it to the construction of a murine craniofacial venous vascular model.Methods A total of nine 8-week-old male C57BL/6 mice weighing (25.0±1.3) g were randomly divided into three groups: 60% latex physiological saline group, 60% latex heparin group, and 30% latex heparin group. After completion of the perfusion, the specimens were immersed in 4 °C formalin fixative for 24 h, followed by dissection, observation, and measurement of the extracranial blood vessel diameters. Results After 200 μL latex perfusion solution was injected into the external jugular vein, the supraorbital vein, infraorbital vein, temporal vein, retrofacial vein, masseter vein and external jugular vein were perfused in each group.After comparing the perfusion degree of the distal branches of blood vessels, sublingual vein and tip venule, it was found that the 30% latex heparin group had the best perfusion effect, followed by the 60% latex heparin group, and the 60% latex saline group had the worst perfusion effect.ConclusionThe optimized latex perfusion technique can effectively infuse the veins in the head and face of mice, and this technique can provide a good reference for the study of the direction and morphology of facial veins in mice.

Objective:To investigate the effects of oocyte maturation trigger using follicle-stimulating hormone (FSH) plus human chorionic gonadotropin (hCG) on clinical outcomes of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in gonadotropin-releasing hormone agonist (GnRH-a) cycles. Methods:The retrospective cohort study included 682 patients aged up to 40 years with normal ovarian response who underwent IVF/ICSI-ET at Department of Reproductive Medicine, Women and Children's Hospital, Xiamen University School of Medicine between Feburary 2016 and April 2017. Patients were grouped by whether oocyte maturation was triggered with 250 μg recombinant hCG (r-hCG) plus 300 U urinary FSH (uFSH, dual trigger group, n=439) or 250 μg r-hCG alone (r-hCG group, n=243). The main observation indexes were the clinical pregnancy rate and the live birth rate, and the secondary observation indexes were the high-quality embryo rate, the implantation rate, the biochemical pregnancy rate, the abortion rate, etc. Results:There were no statistically significant differences between the two groups in age, infertility duration, body mass index (BMI), anti-Müllerian hormone (AMH), total dosage and duration of gonadotropin (Gn) used, number of embryos transferred (all P>0.05). The live birth rate, the clinical pregnancy rate, the miscarriage rate, the normal fertilization rate, the cleavage rate, the embryo formation rate and the high-quality embryo rate were not significantly different between the two groups (all P>0.05). The implantation rate [40.47% (191/472)] and the biochemical pregnancy rate [64.20% (156/243)] were higher in dual trigger group than in r-hCG group [32.42% (272/893), P=0.003; 55.35% (272/893), P=0.025]. Conclusion:Dual trigger of oocyte maturation with 250 μg r-hCG plus 300 U uFSH has no benefit on the clinical pregnancy rate and the live birth rate, but could improve the implantation rate and the biochemical pregnancy rate in women undergoing short-acting GnRH-a protocol in IVF/ICSI-ET.

Objective:To investigate the effects of oocyte maturation trigger using follicle-stimulating hormone (FSH) plus human chorionic gonadotropin (hCG) on clinical outcomes of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) in gonadotropin-releasing hormone agonist (GnRH-a) cycles. Methods:The retrospective cohort study included 682 patients aged up to 40 years with normal ovarian response who underwent IVF/ICSI-ET at Department of Reproductive Medicine, Women and Children's Hospital, Xiamen University School of Medicine between Feburary 2016 and April 2017. Patients were grouped by whether oocyte maturation was triggered with 250 μg recombinant hCG (r-hCG) plus 300 U urinary FSH (uFSH, dual trigger group, n=439) or 250 μg r-hCG alone (r-hCG group, n=243). The main observation indexes were the clinical pregnancy rate and the live birth rate, and the secondary observation indexes were the high-quality embryo rate, the implantation rate, the biochemical pregnancy rate, the abortion rate, etc. Results:There were no statistically significant differences between the two groups in age, infertility duration, body mass index (BMI), anti-Müllerian hormone (AMH), total dosage and duration of gonadotropin (Gn) used, number of embryos transferred (all P>0.05). The live birth rate, the clinical pregnancy rate, the miscarriage rate, the normal fertilization rate, the cleavage rate, the embryo formation rate and the high-quality embryo rate were not significantly different between the two groups (all P>0.05). The implantation rate [40.47% (191/472)] and the biochemical pregnancy rate [64.20% (156/243)] were higher in dual trigger group than in r-hCG group [32.42% (272/893), P=0.003; 55.35% (272/893), P=0.025]. Conclusion:Dual trigger of oocyte maturation with 250 μg r-hCG plus 300 U uFSH has no benefit on the clinical pregnancy rate and the live birth rate, but could improve the implantation rate and the biochemical pregnancy rate in women undergoing short-acting GnRH-a protocol in IVF/ICSI-ET.

Objective:To investigate the causes,prevention and treatment of femoral artery puncture related complications caused by the application of resuscitative endovascular balloon occlusion of the aorta (REBOA) in the resection of pelvic and sacral tumors.Methods:Clinical data of 23 patients with femoral artery puncture related complications who received REBOA in the resection of pelvic and sacral tumors from August 2010 to August 2018 at the Musculoskeletal Tumor Center,Peking University People′s Hospital were retrospectively analyzed.There were 8 males and 15 females,with the age of (37.0±16.2) years (range:15 to 65 years).Arterial access via the Seldinger technique for REBOA was obtained in the right common femoral artery of 18 cases,and in the left of 6 cases.An arterial sheath with a diameter of 11 to 12 F(1 F≈0.33 mm) was used for the patient.The occurrence and treatment of postoperative complications were analyzed.Results:Acute femoral arterial thrombosis occurred in 18 patients,which was managed by open repair 48 hours postoperatively.Among the 349 patients admitted before 2015 who received hemostasis by compression after femoral artery sheath removal,12 patients (3.4%) developed acute femoral artery thrombosis.While the 476 patients admitted after 2015 who used a percutaneous suture device to close the femoral artery wound,6 patients (1.3%) developed acute femoral artery thrombosis.One case of retroperitoneal hematoma and 1 case of femoral pseudoaneurysm were found and surgically fixed.Postoperative follow-up was (40±18) months (range:13 to 108 months).Three cases with chronic lower extremity ischemia were confirmed by Doppler ultrasonography during 1 to 5 years follow-up.Two of them had minimal symptoms and denied further treatment,while the other one received femoral-femoral artery bypass surgery to restore distal flow for pain and numbness relief.Conclusions:Acute femoral arterial thrombosis is the most common femoral artery puncture.Technique refinement of REBOA,the use of percutaneous suture device and close follow-up can reduce the approach-specific complications,and help to detect and treat the complications timely,which may popularize the clinical application of REBOA.

Objective:To investigate the causes,prevention and treatment of femoral artery puncture related complications caused by the application of resuscitative endovascular balloon occlusion of the aorta (REBOA) in the resection of pelvic and sacral tumors.Methods:Clinical data of 23 patients with femoral artery puncture related complications who received REBOA in the resection of pelvic and sacral tumors from August 2010 to August 2018 at the Musculoskeletal Tumor Center,Peking University People′s Hospital were retrospectively analyzed.There were 8 males and 15 females,with the age of (37.0±16.2) years (range:15 to 65 years).Arterial access via the Seldinger technique for REBOA was obtained in the right common femoral artery of 18 cases,and in the left of 6 cases.An arterial sheath with a diameter of 11 to 12 F(1 F≈0.33 mm) was used for the patient.The occurrence and treatment of postoperative complications were analyzed.Results:Acute femoral arterial thrombosis occurred in 18 patients,which was managed by open repair 48 hours postoperatively.Among the 349 patients admitted before 2015 who received hemostasis by compression after femoral artery sheath removal,12 patients (3.4%) developed acute femoral artery thrombosis.While the 476 patients admitted after 2015 who used a percutaneous suture device to close the femoral artery wound,6 patients (1.3%) developed acute femoral artery thrombosis.One case of retroperitoneal hematoma and 1 case of femoral pseudoaneurysm were found and surgically fixed.Postoperative follow-up was (40±18) months (range:13 to 108 months).Three cases with chronic lower extremity ischemia were confirmed by Doppler ultrasonography during 1 to 5 years follow-up.Two of them had minimal symptoms and denied further treatment,while the other one received femoral-femoral artery bypass surgery to restore distal flow for pain and numbness relief.Conclusions:Acute femoral arterial thrombosis is the most common femoral artery puncture.Technique refinement of REBOA,the use of percutaneous suture device and close follow-up can reduce the approach-specific complications,and help to detect and treat the complications timely,which may popularize the clinical application of REBOA.

Objective: To assess the value of dry blood spot tandem mass spectrometry for the diagnosis of autism spectrum disorder (ASD). Methods: Peripheral blood samples of 277 autistic children were collected. Their amino acid and carnitine profiles were detected by liquid chromatography tandem mass spectrometry. Urine samples of suspected patients were collected for verification by gas chromatography mass spectrometry. Blood samples were also taken for genetic testing. Results: Of the 277 children with ASD, 19 (6.9%) were suspected to be with inborn error of metabolism (IEM), which included 6 cases with amino acidemia, 9 with organic acidemia and 4 with fatty acidemia. Three cases of phenylketonuria, one case of homocysteinemia, one case of propionemia, one case of methylmalonic acidemia, one case of glutaric acidemia, one case of isovaleric acidemia, one case of argininemia, one case of citrullinemia I and four cases of primary carnitine deficiency were confirmed by genetic testing, which yielded an overall diagnostic rate of 5.1% (14/277). Conclusion Our result has provided further evidence for the co-occurrence of ASD and IEM. Tandem mass spectrometry has a great value for the diagnosis and treatment of ASD in childhood.

BACKGROUND/AIMS: Gastrointestinal (GI) symptoms may develop when we fail to adapt to various stressors of our daily life. Central oxytocin (OXT) can counteract the biological actions of corticotropin-releasing factor (CRF), and in turn attenuates stress responses. Administration (intracerebroventricular) of OXT significantly antagonized the inhibitory effects of chronic complicated stress (CCS) on GI dysmotility in rats. However, intracerebroventricular administration is an invasive pathway. Intranasal administration can rapidly deliver peptides to the brain avoiding stress response. The effects of intranasal OXT on hypothalamus-pituitary-adrenal axis and GI motility in CCS conditions have not been investigated. METHODS: A CCS rat model was set up, OXT 5, 10, or 20 μg were intranasal administered, 30 minutes prior to stress loading. Central CRF and OXT expression levels were analyzed, serum corticosterone and OXT concentrations were measured, and gastric and colonic motor functions were evaluated by gastric emptying, fecal pellet output, and motility recording system. RESULTS: Rats in CCS condition showed significantly increased CRF expression and corticosterone concentration, which resulted in delayed gastric emptying and increased fecal pellet output, attenuated gastric motility and enhanced colonic motility were also recorded. OXT 10 μg or 20 μg significantly reduced CRF mRNA expression and the corticosterone concentration, OXT 20 μg also helped to restore GI motor dysfunction induced by CCS. CONCLUSION: Intranasal administration of OXT has an anxiolytic effect and attenuates the hypothalamus-pituitary-adrenal axis in response to CCS, and gave effects which helped to restore GI dysmotility, and might be a new approach for the treatment of stress-induced GI motility disorders.
Administration, Intranasal ; Animals ; Anti-Anxiety Agents ; Brain ; Colon ; Corticosterone ; Corticotropin-Releasing Hormone ; Gastric Emptying ; Gastrointestinal Motility ; Models, Animal ; Oxytocin ; Peptides ; Rats ; RNA, Messenger

OBJECTIVE: To assess the value of dry blood spot tandem mass spectrometry for the diagnosis of autism spectrum disorder (ASD). METHODS: Peripheral blood samples of 277 autistic children were collected. Their amino acid and carnitine profiles were detected by liquid chromatography tandem mass spectrometry. Urine samples of suspected patients were collected for verification by gas chromatography mass spectrometry. Blood samples were also taken for genetic testing. RESULTS: Of the 277 children with ASD, 19 (6.9%) were suspected to be with inborn error of metabolism (IEM), which included 6 cases with amino acidemia, 9 with organic acidemia and 4 with fatty acidemia. Three cases of phenylketonuria, one case of homocysteinemia, one case of propionemia, one case of methylmalonic acidemia, one case of glutaric acidemia, one case of isovaleric acidemia, one case of argininemia, one case of citrullinemia I and four cases of primary carnitine deficiency were confirmed by genetic testing, which yielded an overall diagnostic rate of 5.1% (14/277). CONCLUSION Our result has provided further evidence for the co-occurrence of ASD and IEM. Tandem mass spectrometry has a great value for the diagnosis and treatment of ASD in childhood.
Amino Acid Metabolism, Inborn Errors ; complications ; diagnosis ; Autism Spectrum Disorder ; complications ; diagnosis ; Child ; Dried Blood Spot Testing ; Gas Chromatography-Mass Spectrometry ; Humans ; Metabolism, Inborn Errors ; complications ; diagnosis ; Tandem Mass Spectrometry

PURPOSE: Allergic rhinitis (AR) has become a global issue for a large part of the general population. Sublingual immunotherapy (SLIT) has been used extensively to treat persistent allergic rhinitis (PAR). Although systematic reviews have confirmed the effectiveness of SLIT for the treatment of AR, a considerable number of studies using extracts of house dust mites (HDMs) for immunotherapy found no consensus on basic treatment parameters and questioned the efficacy of SLIT. METHODS: In this study, we evaluated SLIT for PAR by a meta-analysis of randomized controlled trials (RCTs). Medline, Embase, and Cochrane Library database searches were performed for RCTs on the treatment of PAR by SLIT that assessed clinical outcomes related to efficacy through May 2016. Descriptive and quantitative information was abstracted. An analysis was performed with standardized mean differences (SMDs) under a fixed or random effects model. Subgroup analyses were performed. Heterogeneity was assessed using the I2 metric. RESULTS: In total, 25 studies were eligible for inclusion in the meta-analysis for symptom scores and 15 studies for medication scores. SLIT was significantly different from the controls for symptom scores (SMD=1.23; 95% confidence interval [CI]=1.74 to 0.73; P<0.001). For medication scores, significant differences for SLIT were also observed versus the controls (SMD=-1.39; 95% CI=-1.90 to -0.88; P<0.001). CONCLUSIONS: Our meta-analysis indicates that SLIT provided significant symptom relief and reduced the need for medications in PAR. In this study, significant evidence was obtained despite heterogeneity with regard to the use of mite extract. Specifically, the mite extract used was provided by the patients with PAR. Furthermore, to confirm both the objective outcomes and the effective doses of HDM allergen extracts, experimental data should be obtained from large high-quality population-based studies.
Consensus ; Dust* ; Humans ; Immunotherapy ; Mites ; Population Characteristics ; Pyroglyphidae ; Rhinitis, Allergic* ; Sublingual Immunotherapy*