Objective To compare the clinical outcomes of gonadotropin-releasing hormone (GnRH) antagonist (GnRH-ant) fixed protocol with GnRH agonist (GnRH-a) long protocol in infertile patients with normal ovarian reserve function in their first in vitro fertilization-embryo transfer (IVF-ET) cycle,and to explore the feasibility and advantage of GnRH antagonist protocol performed in normal responders.MethodsFrom January 2011 to June 2011,771 infertile women with normal ovarian reserve function underwent their first IVF or intracytoplasmic sperm injection (ICSI) cycles in Peking University Third Hospital,which were divided into 245 cycles in GnRH-ant fixed protocol group ( GnRH-ant group) and 526 cycles in GnRH-a long protocol group ( GnRH-a group).The data of general demographic,treatment and clinical outcome were compared between two groups.ResultsAge,infertile duration,body mass index (BMI),baseline serum follicle-stimulating hormone (FSH) and estradiol levels between two groups did not reached statistical difference (P ＞ 0.05 ).The level of estradiol was (12 289 ± 6856) pmol/L in GnRH-ant group and (14934±8007)pmol/L in GnRH-a group at day of hCG injection.The mean length of stimulation was ( 10.3 ± 1.2) days in GnRH-ant group and ( 12.8 ± 1.6) days in GnRH-a group.The dose of gonadotropin was (2013 ± 607 ) U in GnRH-ant group and (2646 ± 913 ) U in GnRH-a group.The number of ovum was 15 ± 7 in GnRH-ant group and 17 ± 8 in GnRh-a group.Those clinical parameter all reached statistical difference (P ＜0.05 ).The number of embryo was 7 ±4 in GnRH-ant group and 8 ± 5 in GnRH-a group,the rate of clinical pregnancy was 40.9％ (94/230) in GnRH-ant group and 45.6％ (216/474)in GnRH-a group,the rate of implantation was 26.1％ (128/490)in GnRH-ant group and 30.9％ (307/994) in GnRH-a group,the rate of continuing pregnancy was 38.7％ ( 89/230 ) in GnRH-ant group and 42.6％ (202/474) in GnRH-a group,those parameter did not reach statistical difference (P ＞ 0.05).The rate of moderate or severe ovarian hyperstimulation syndrome was 2.4％ ( 6/245 ) in GnRH-ant group and 4.2％ (22/526) in GnRH-a group,which did not show significant difference ( P ＞ 0.05 ).ConclusionIn the first IVF or ICSI cycle of the patients with normal ovarian reserve function,the fixed GnRH-ant protocol could get the same satisfied clinical outcome,and it is more economic,convenient and safer compared with low dose depot GnRH-a long protocol.

Objective:To summarize the clinical characteristics, diagnosis and treatment of caspase recruitment domain-containing protein 9 (CARD9) gene deficiency associated invasive candidiasis, and report a novel mutation in CARD9 gene.Methods:The clinical characteristics, laboratory tests, treatment and the outcome of follow-up in a boy with invasive candidiasis were described. The boy′s main clinical manifestations were central nervous system infection and retroperitoneal mass. Whole-exome sequencing was performed and Sanger sequencing was verified to identify the CARD9 gene mutations in the patient and his parents. A literature search for “CARD9”and “invasive candidiasis”was conducted in PubMed, Wanfang and CNKI databases from their establishment to May 2020.Results:A 10-year-old boy suffered onset symptom of chronic diarrhea, which lasted for two months. The symptom was followed by progressive neurological symptoms such as headache, vomiting, seizures and disorder of consciousness. His unusual medical history was absent. Candida albicans were cultured several times in cerebrospinal fluid and blood, and yeast-like fungi were found in the stool high power field of vision. Cerebral magnetic resonance imaging indicated obstructive hydrocephalus and abdominal CT scan showed retroperitoneal mass and thickening of the intestinal wall. The whole-exome sequencing analyses of blood samples from the boy and his parents were performed. The results showed that there was a homozygous mutation of c.952-12_956delinsAG in the CARD9 gene, which was an unreported pathogenic mutation. This was confirmed by Sanger sequencing. There was no significant relief from intravenous combined antifungal medications. After lateral ventricular drainage surgery and injection of amphotericin B into the lateral ventricle, improvement of clinical symptoms and cerebral spinal fluid abnormalities was observed after nine weeks, and the retroperitoneal mass shrank. At follow-up after four-month oral combined antifungal medications, the child had no complaint except fatigue. However, cerebral spinal fluid analysis showed increased protein level and decreased glucose. Persistent hydrocephalus and periventricular white matter abnormal signals were revealed on the brain magnetic resonance imaging and the smaller retroperitoneal mass than before on the abdominal CT scan. In addition to this case, totally 21 cases with CARD9 gene deficiency associated invasive candidiasis have been reported worldwide, most of which featured central nervous system infections.Conclusions:CARD9 gene deficiency is an autosomal recessive primary immunodeficiency that confers human susceptibility to fungal disease. The associated invasive candidiasis often affects the central nervous system and makes the patient severely ill. Adequate systemic antifungal therapies should be given, and patients with hydrocephalus need surgical treatment. A novel mutation is reported that expands the variant diversity of CARD9 gene. For patients with unexplained invasive candidiasis, including those without a history of previous recurrent infection, genetic testing is recommended for primary immunodeficiency including CARD9 gene deficiency.

Air ; analysis ; Alcohols ; analysis ; Electrophoresis, Capillary ; Workplace

Objective To investigate clinical and pathological characteristics of insulin-induced localized lipoatrophy and treatment.Methods We retrospectively analyzed clinical manifestation, skin biopsy pathology, treatment regimen and follow-up of 6 diabetic patients with insulin-induced localized lipoatrophy in Peking Union Medical College Hospital from January, 2010 to March, 2016, with systemic review of related literatures.Results Among 6 cases with insulin-induced localized lipoatrophy, 5 patients were with insulin allergy.5 patients were with positive insulin-autoimmune antibody, which was similar to the ratio reported in the systematic review (18 out of 19).Insulin-induced lipoatrophy could be caused by various types of preparations of insulin and insulin analogs.Subcutaneous biopsy, performed on the atrophied area, revealed the decrease of the number and volume of adipocytes and tissue fibrosis, probably accompanied with lymphocytes, eosinophils or mast cells infiltration.Lipoatrophy could sometimes be relieved by changing injection sites, types of insulin preparations or drug-delivery way, sometimes by application of systemic/local glucocorticoid or local cromolyn sodium.Conclusions Insulin-induced localized lipoatrophy is a rare adverse reaction of insulin preparations.It might be related to immune response of local tissue and heterogeneous pathological manifestations.The lipoatrophy might be improved by changing injection sites, changing the type of insulin preparations or drug-delivery way, and with possibility to carry out targeted immunosuppressive therapy according to the biopsy pathology in the future.

Objective:To observe the clinical characteristics of paroxysmal sympathetic hyperactivity (PSH) in children with acute brain injury.Methods:The clinical characteristics, hospitalization data, hospitalization cost, and prognoses of 40 children with acute brain injury admitted to our hospital from June 2018 to June 2020 were retrospectively summarized. In addition, the differences of above data between children with PSH and children without PSH were comparatively analyzed.Results:Nine children were with PSH, with an incidence of 22.5%; five were with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis, two were with acute necrotizing encephalopathy, and two were with severe viral encephalitis. Thirty-one children were without PSH; five were with metabolic encephalopathy, 19 were with viral encephalitis, three were with anti-NMDAR encephalitis, one was with acute cerebral infarction, one was with primary central nervous system lymphoma, one was with acute necrotizing encephalopathy, and one was with severe closed head injury. The patients with PSH had significantly higher proportion of patients with anti-NMDAR encephalitis, significantly higher hospitalization cost, statistically longer duration of disorder of consciousness and hospital stays, and significantly lower Glasgow coma scale (GCS) scores at discharge than the patients without PSH ( P<0.05). Conclusion:PSH is common in children with acute brain injury; PSH can lead to a long period of disorders of consciousness, long hospital stays, high hospitalization cost, and poor prognosis, which causes an increase in family and social burdens.

AIMTo study the effect of angiotensin-(1-7) on the kidney of diabetic rats by observing the mRNA expression of PDGF and TGF-beta1.

METHODSSD rats were divided into three groups: Group C (uni-nephrectomy control group), Group D (diabetic model control group), Group T (Ang-(1-7) treated group). We evaluated blood glucose,urea nitrogen, creatinine and urine albumin excretion respectively, studied the renal morphology by light microscope, and detected the gene expression of PDGF, TGF-beta1 in renal tissue by RT-PCR technique.

RESULTSThere was significant difference between the group D and T about the RW/BW, renal morphology, the total urine protein and the mRNA expression of PDGF and TGF-beta1.

CONCLUSIONAng-(1-7) can relieve the renal process of diabetic rats.

Angiotensin I ; pharmacology ; Animals ; Diabetes Mellitus, Experimental ; metabolism ; Diabetic Nephropathies ; metabolism ; Kidney ; metabolism ; pathology ; Male ; Peptide Fragments ; pharmacology ; Platelet-Derived Growth Factor ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; genetics ; metabolism

BACKGROUNDCategory III chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common syndrome of unclear etiology with significant impact on quality of life. Because the outcomes of multiple therapies for CP/CPPS have been far from approving, the possible psychological factors have been considered to play an important role in CP/CPPS. Based on this, we investigated the role of antidepressant drug (fluoxetine) in men with refractory CP/CPPS.

METHODSIn this study, 42 men diagnosed with refractory CP/CPPS without response to standard therapy (include multiple antibiotic courses and α-blockers) were referred for fluoxetine therapy. All patients received fluoxetine (20 mg/d) for three months and were clinically evaluated before (baseline), and after 4, 8 and 12 weeks of therapy. The evaluation included a National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) and a Beck depression inventory (BDI) questionnaire. Moreover, the subjective global assessment (SGA) was assessed at the 4th, 8th and 12th week of therapy.

RESULTSSignificant decreases were observed for total NIH-CPSI (28.55 to 9.29), NIH-CPSI pain (14.69 to 5.19), NIH-CPSI urinary (4.95 to 1.88), NIH-CPSI quality of life (8.83 to 2.20), and BDI (34.67 to 13.95) scores compared with baseline, all P values < 0.05. Twenty-nine (69.05%) reported marked improvement on the subjective global assessment and 33 (78.57%) had a greater than 50% decrease in NIH-CPSI at the end of therapy (12th week). At the same time, the Pearson correlation coefficient analysis demonstrated a positive correlation between BDI score and each CPSI score. No adverse events were reported in this study.

CONCLUSIONSFluoxetine appears to be a safe and effective treatment in improving symptoms in, and the quality of life of, men with difficult CP/CPPS. Moreover, amelioration of difficult CP/CPPS-related symptoms could be related to a decrease in depressive symptoms.

Adult ; Antidepressive Agents, Second-Generation ; adverse effects ; therapeutic use ; Chronic Disease ; Fluoxetine ; adverse effects ; therapeutic use ; Humans ; Male ; Middle Aged ; Pelvic Pain ; drug therapy ; Prostatitis ; drug therapy ; Quality of Life ; Treatment Outcome ; Young Adult

Objective To investigate the changes of tight junction (TJ) protein occludin expression between the mierovascular endothelial cells of the blood-brain barrier (BBB) of rats after intracerebral hemorrhage (ICH). Methods Ninety-three male SD rats were randomly divided into normal control group and experimental group; rats of the experimental group were divided into 6 subgroups (6, 24, 48 and 72 h, and 7 and 14 d after intraeerebral hemorrhage). Rat models of intracerebral hemorrhage in the experimental group were established by autologous blood injection.Morphology of the brain tissues was detected by hematoxylin-eosin (HE) staining.The tight junctions between the microvascular endothelial cells of the BBB were sampled for ultrastructural observation using electron microcopy.Immunofluorescence and quantitative real time-PCR were used to analyze the protein and mRNA expressions of occludin,respectively. Results The brain edema was found in brain tissues around the hematoma. Necrosis and inflammatory infiltration could be found in perihematomal brain tissues and it was most obvious at 48 h after intracerebral hemorrhage. Obvious paracellular clefts were found between the adjacent endothelial cells in experimental groups. Strong expression of occludin was noted in the normal brain tissue; expression of occludin was positive 6 h after the injection and weak positive at 24, 48 and 72 h after the injection in the experimental groups.Quantitative real time-PCR showed that the mRNA expression of occludin in the experimental group was significantly reduced as compared with the normal brain tissue at 6,24,48 and 72 h after the injection with statistically significant difference (P＜0.05). Conclusion After intra-cerebral hemorrhage,as a major component of TJ of the BBB,occludin expression is down-regulated,which may be one of the most impotant molecular basis of disruption of BBB.

[Objective]To explore the distribution and expression changes of tight junctional protein JAM-1 in rat models after intracerebral hemorrhage (ICH) and their significance.[Methods]One hundred and twenty-eighty healthy male SD rats were randomly divided into normal control group (n=16) and ICH group (n=112),and the ICH models were induced by stereotactically injecting 75 uL autologous blood into the right caudate nucleus.Seven time points after ICH (6,12,24 and 48 h,and 3,7 and 14 d after ICH,16 rats for each time point) were chosen.BBB permeability was evaluated by Evans blue dye extravasation.The distribution and expression of JAM-1 were detected by immunofluorescence and real-time quantitative PCR.[Results] As compared with that in the normal control group,BBB permeability in the ICH group significantly increased at 24 and 48 h,and 3 and 7 d after ICH (P＜0.05).JAM-1 expression decreased at blood vessels at 12,24 and 48 h after ICH,and JAM-1 expressed at the circulatingleukocytes3 dafterlCH,and abundant JAM-1 positive cells around hematoma were noted in the ED-l-positve macrophages 7 d after ICH.JAM-I mRNA significantly decreased at 12,24 and 48 h after ICH,and significantly increased 7 d after ICH as compared with that in the normal control group (P＜0.05).[Conclusion] JAM-1 experssion changes not only participate in regulation of BBB permeability but also play roles in inflammatory insult after ICH.

BACKGROUNDEndogenous nitric oxide and adenosine increase simultaneously to keep the balance of energy demand and supply when the oxygen supply is insufficient, which suggests that nitric oxide and adenosine might exert a synergistic myoprotection during tissue hypoxia. In this study, we tested this hypothesis utilizing a canine model of prolonged global myocardial ischaemic reperfusion injury.

METHODSIn this double blind, controlled study, the hearts of 24 anaesthetized mongrel dogs were arrested for 2 hours with aortic cross clamping and blood cardioplegia. The treatment groups were those supplemented with 2 mmol/L L-arginine (ARG), supplemented with 1 mmol/L adenosine (ADO), ARG + ADO supplemented with both, and no supplementation (control) (n = 6 in each group). Haemodynamics, biochemical indices, adenosine triphosphate (ATP) content and myeloperoxidase activities of myocardium were determined to evaluate myocardial injury. Statistical comparison was performed by two way ANOVA.

RESULTSAlthough the requirements for inotropic supports were higher, the cardiac outputs were lower in control group than in ARG, ADO and the combination groups. Plasma cardiac troponin I levels were higher and the areas of hydropic changes were larger in control group than in ARG and ADO groups. Combination of arginine and adenosine provided further myoprotection with respect to better cardiac performance, lower release of cardiac troponin I, and smaller areas of hydropic changes compared with ARG and ADO groups. ATP content was higher, but myeloperoxidase activities of myocardium were significantly lower in the combination group than in control, ARG and ADO groups (P < 0.05).

CONCLUSIONSCombination of L-arginine and adenosine provides synergistic myoprotection in a canine model of global myocardial ischaemia. Thus, the combination is recommended when the heart is exposed to a prolonged ischaemia during cardiac surgery.

Adenosine ; therapeutic use ; Adenosine Triphosphate ; analysis ; Animals ; Arginine ; therapeutic use ; Cardiotonic Agents ; therapeutic use ; Disease Models, Animal ; Dogs ; Drug Synergism ; Energy Metabolism ; Female ; Heart Arrest, Induced ; Male ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; metabolism ; pathology ; Peroxidase ; metabolism