Biallelic mutations in spermatogenesis and centriole-associated 1 like (SPATC1L) cause acephalic spermatozoa syndrome and male infertility / 亚洲男科学杂志(英文版)

Acephalic spermatozoa syndrome is a rare type of teratozoospermia that severely impairs the reproductive ability of male patients, and genetic defects have been recognized as the main cause of acephalic spermatozoa syndrome. Spermatogenesis and centriole-associated 1 like (SPATC1L) is indispensable for maintaining the integrity of sperm head-to-tail connections in mice, but its roles in human sperm and early embryonic development remain largely unknown. Herein, we conducted whole-exome sequencing (WES) of 22 infertile men with acephalic spermatozoa syndrome. An in silico analysis of the candidate variants was conducted, and WES data analysis was performed using another cohort consisting of 34 patients with acephalic spermatozoa syndrome and 25 control subjects with proven fertility. We identified biallelic mutations in SPATC1L (c.910C>T:p.Arg304Cys and c.994G>T:p.Glu332X) from a patient whose sperm displayed complete acephalia. Both SPATC1L variants are rare and deleterious. SPATC1L is mainly expressed at the head-tail junction of elongating spermatids. Plasmids containing pathogenic variants decreased the level of SPATC1L in vitro. Moreover, none of the patient's four attempts at intracytoplasmic sperm injection (ICSI) resulted in a transplantable embryo, which suggests that SPATC1L defects might affect early embryonic development. In conclusion, this study provides the first identification of SPATC1L as a novel gene for human acephalic spermatozoa syndrome. Furthermore, WES might be applied for patients with acephalic spermatozoa syndrome who exhibit reiterative ICSI failures.

Application of teaching and anti-teaching system in clinical skills teaching of the standardized residency training / 中华医学教育探索杂志

Objective:To explore the application and effect of teaching and anti-teaching system in clinical skills teaching of the standardized residents training.Methods:Forty pediatric residents of Batch 2018 in Hunan Children's Hospital were randomly divided into the conventional teaching group and the teaching and anti-teaching teaching group, 20 in each group. All of them received the skills training for medical licensing examination. A comparative analysis of the teachers' on-site training time, and the time of mastering individual skill, the skill operation ability, and the comprehensive ability in the two groups was conducted. In addition, teachers and students' satisfaction with teaching and anti-teaching system was investigated by Wenjuanxing, a platform providing questionnaire survey. SPSS 17.0 software was used for t-test and Chi-square test. Results:The teachers' on-site training time [(21.75±3.24) min vs. (48.65±2.91) min] and the residents' time of mastering skills and knowledge [(20.46±3.57) min vs. (30.24±4.73) min] in the teaching and anti-teaching teaching group were shorter than those in the conventional teaching group ( P < 0.05). The scores of clinical skills [(92.96±5.21) points vs. (84.13±3.28) points] and the comprehensive ability [(91.23±5.06) points vs. (85.23±5.72) points] of the residents in the teaching and anti-teaching teaching group were higher than those in the conventional teaching group ( P<0.05). The questionnaire survey showed that the residents had a positive attitude towards the teaching and anti-teaching teaching. They believed that it had the advantage of facilitating full-dimensional viewing of the operation, improving the learning interest, and achieving better learning effect for the residents. Conclusion:The application of teaching and anti-teaching system in the standardized training of residents in children's hospitals can make up for the rare adult clinical operation learning opportunities in children's hospitals, rapidly improve the professional skills of residents, improve the passing rate of medical licensing examination, and help to improve the post competency of residents.

Serum procalcitonin and C-reactive protein in the evaluation of bacterial infection in generalized pustular psoriasis

Abstract Background There is an obvious need for more prompt and specific biomarkers of bacterial infections in generalized pustular psoriasis patients. Objective The aim of this study was to evaluate the diagnostic properties and define appropriate cut-off values of procalcitonin and C-reactive protein in predicting bacterial infection in generalized pustular psoriasis patients. Methods Sixty-four generalized pustular psoriasis patients hospitalized from June 2014 to May 2017 were included in this retrospective study. The values of procalcitonin, C-reactive protein, details of infection, and other clinical parameters were analyzed. Results Receiver operating characteristic curve analysis generated similar areas (p = 0.051) under the curve for procalcitonin 0.896 (95% CI 0.782-1.000) and C-reactive protein 0.748 (95% CI 0.613-0.883). A cut-off value of 1.50 ng/mL for procalcitonin and 46.75 mg/dL for C-reactive protein gave the best combination of sensitivity (75.0% for procalcitonin, 91.7% for C-reactive protein) and specificity (100% for procalcitonin, 53.8% for C-reactive protein). Procalcitonin was significantly positively correlated with C-reactive protein levels both in the infected (r = 0.843, p = 0.040) and non-infected group (r = 0.799, p = 0.000). Study limitations The sample size and the retrospective design are limitations. Conclusions The serum levels of procalcitonin and C-reactive protein performed equally well to differentiate bacterial infection from non-infection in generalized pustular psoriasis patients. The reference value of procalcitonin and C-reactive protein applied to predicting bacterial infection in most clinical cases may not be suitable for generalized pustular psoriasis patients. C-reactive protein had better diagnostic sensitivity than procalcitonin; however, the specificity of procalcitonin was superior to that of C-reactive protein.

Relationship between plasma lipoprotein associated phospholipase A2 and coronary in-stent restenosis after percutaneous coronary intervention / 天津医药

@# Objective ToinvestigatetherelationshipbetweenplasmalipoproteinassociatedphospholipaseA2(LpPLA2)levelandin-stentrestenosis(ISR)afterpercutaneouscoronaryintervention(PCI).Methods Atotalof208patients treatedwithPCIandexaminedwithafollow-upcoronaryangiograph(CAG)wereincludedinthisstudy.Thepatientswere dividedinto2groupsbasedontheresultsofISRcondition:ISRgroup(n=29)andNISRgroup(n=179).Theplasmalevelsof Lp-PLA2weredetectedbeforefirst-PCIoperationandfollow-upCAGintwogroups.Thegeneralclinicaldata,biochemical parameters,coronarycoronariography,interventionalfeaturesandplasmalevelsofLp-PLA2werecomparedbetweenthetwo groups.LogisticregressionanalysiswasusedtoanalyzetheindependentriskfactorforISR.Receiveroperatingcharacteristic curvewasusedtoevaluatethepredictiveabilityoftheplasmalevelofLp-PLA2totheoccurrenceofISR.Results (1)In ISRgroup,patientswiththehistoryoftype2diabetes,levelsoflowdensitylipoproteincholesterol(LDL-C)andlevelsof glycosylatedhemoglobin(HbA1c)weresignificantlyhigherthanthoseinNISRgroup,whileserumlevelsoftotalbilirubin(TBIL)decreased,thelengthofthestentwaslonger,andstentdiameterwassmaller(P＜0.05).(2)InISRgroup,theLp-PLA2 level and ΔLp-PLA2 level were higher before first-PCI operation than those in NISR group (P＜0.05). (3) Logistic regressionanalysisshowedthatT-BIL,stentdiameterandΔLp-PLA2weretheindependentriskfactorsforISR(P＜0.05). (4)Thereceiveroperatingcharacteristiccurve(ROC)areaofΔLp-PLA2forpredictingpost-PCIISRoccurrencewas0.862, theoptimalcutoffvalueofΔLp-PLA2was20.68μg/L,thesensitivitywas79%,andthespecificitywas83%.Conclusion TheincreasedlevelofLp-PLA2afterPCIiscorrelatedwithISR,andtheregularmonitoringthelevelofLp-PLA2hassome significanceinforecastingISR.

An association study of single nucleotide polymorphisms of the FOXP3 intron-1 and the risk of Psoriasis vulgaris.

Psoriasis vulgaris (PV) is a common autoimmune disease that involves the dysfunction of CD4+CD25+ regulatory T cells. FOXP3 is a key transcription factor in the development and function of CD4+CD25+ regulatory T cells. Previous studies have demonstrated a genetic association between the FOXP3 gene and some autoimmune diseases. To elucidate the association between the FOXP3 gene and the risk of PV, 408 patients diagnosed with PV and 363 age and sex-matched healthy controls from a cohort of the Chinese majority Han population were recruited. Four single nucleotide polymorphisms (rs2232365, rs3761547, rs3761548 and rs3761549) of the FOXP3 gene were analyzed using the polymerase chain reaction and ligase detection reaction. The major allele of three single nucleotide polymorphisms (SNPs — rs2232365 A, rs3761547 A and rs3761549 C) were associated with an increased risk of PV in a clinical subgroup of female patients, who were less than 40 yrs of age, had a family history of the disease and did not have disease complications (p < 0.05 for all parameters). The haplotype was structured between rs3761547 and rs3761549. An increased risk of PV was observed in haplotype A/A-T/T (p = 0.0055; adjusted OR = 3.188; 95% CI = 0.4354-23.34) and A/G-C/C (p = 0.0082; adjusted OR = 1.288; 95% CI = 0.1529-10.85) between rs3761547 and rs3761549. A synergistic effect was found among the three SNPs. Subjects with the rs2232365AA- rs3761547 AG + GG genotype were more susceptible to PV (p = 0.0393; OR = 2.90; 95% CI = 1.05-7.97). No correlation was found between rs3761548 and the onset of PV. Therefore, the FOXP3 polymorphisms appear to contribute to the risk of psoriasis among the Chinese majority Han population. These findings may aid in our understanding of the pathogenesis of psoriasis

No spatial memory deficit exists in Kunming mice that recently recovered from motor defects following 3-nitropropionic acid intoxication / 神经科学通报·英文版

<p><b>OBJECTIVE</b>Numerous studies have described both motor defects and cognitive impairments in several strains of rodents following 3-nitropropionic acid (3-NP) intoxication. In the present study, we investigated spatial recognition memory in Kunming mice that just recovered from motor defects induced by 3-NP.</p><p><b>METHODS</b>Mouse model was made by systemic subacute 3-NP treatment, and spatial recognition memory was measured through the Y-maze Test, a simple two-trial recognition test.</p><p><b>RESULTS</b>(1) On day 15 following 3-NP treatment, affected Kunming mice did not show motor defects in the Rotarod test and presented normal gait again. (2) In the following Y-maze test after 1h interval, the percentage (90.0%) of mice showing novel arm preference in 3-NP treatment group was significantly higher than the random chance level (50%), although it was only slightly higher than that (83.3%) in control group. On day 45 after 3-NP treatment, mice failed to choose unfamiliar novel arm as first choice, and the same occured in the control group. (3) For both post-intoxicated (on day 15 and day 45 following 3-NP treatment) and control groups, the duration in the novel arm and the frequency of entering it, were longer and higher compared with familiar start and other arms. For these mice that recently recovered from motor defects following 3-NP intoxication, no spatial memory deficits were observed through Y-maze Test.</p><p><b>CONCLUSION</b>Kunming mice used in our assays might possess resistance to cognitive impairment induced by 3-NP, which is consistent with previous findings in Swiss EPM-M1 mice.</p>

Polymorphism of the catechol-O-methyltransferase gene in Han Chinese patients with psoriasis vulgaris

Psoriasis vulgaris is defined by a series of linked cellular changes in the skin: hyperplasia of epidermal keratinocytes, vascular hyperplasia and ectasia, and infiltration of T lymphocytes, neutrophils and other types of leukocytes in the affected skin. Catechol-O-methyltransferase (COMT) 158 polymorphism can reduce the activity of the COMT enzyme that may trigger defective differentiation of keratinocytes in psoriasis. Immunocytes can degrade and inactivate catecholamines via monamine oxidase (MAO) and COMT in the cells. We hypothesized that the COMT-158G > A polymorphism was associated with the risk of psoriasis vulgaris in Han Chinese people. In a hospital-based case-control study, 524 patients with psoriasis vulgaris and 549 psoriasis-free controls were studied. COMT-158 G > A polymorphism was genotyped using the PCR sequence-specific primer (PCR-SSP) technique. We found no statistically significant association between the COMT-158 allele A and the risk of psoriasis vulgaris (p = 0.739 adjusted OR = 1.03; 95% CI = 0.81-1.31). This suggests that the COMT-158 G > A polymorphism may not contribute to the etiology of psoriasis vulgaris in the Han Chinese population.

Is CCR7 a potential target for biologic therapy in psoriasis?: Increased expression of CCR7 in psoriasis vulgaris.

BACKGROUND: Activated T cells present in psoriatic plaques play a key role in the pathogenesis of psoriasis. CCR7 on T cells plays a crucial role in native immune response and formation of secondary lymphoid organ. AIMS: To determine whether differential expression and functions of the CCR7 occur in psoriasis patients in China, we examined CCR7 on T cells from normal and psoriasis subjects. METHODS: Skin specimens and T cells from 33 patients and 22 healthy controls were analyzed by immunohistology, flow cytometry, and RT-PCR. RESULTS: Patients with psoriasis had a skewed distribution of T lymphocytes, with an increased level of CCR7+ T lymphocytes compared to healthy controls (P<0.01) By flow cytometry, it was found that CCR7 was selectively, frequently, and functionally expressed on CD4+ (20.5+/-6.8%)but not on CD8+ (9.5+/-3.4%) T cells from patients with psoriasis, whereas this phenomenon was not seen in normal subjects. Through RT-PCR it was also found that CCR7 was highly expressed on T cells in patients with psoriasis than in healthy controls in the level of gene. CONCLUSIONS: Patients with psoriasis had a skewed distribution of T lymphocytes, with an increased level of CCR7+ T lymphocytes compared to healthy controls. CD4+ CCR7+ T cells had abnormal expression, which might induce protraction and persistence of psoriasis.

Depressive-like behavior in mice recently recovered from motor disorders after 3-nitropropionic acid intoxication / 神经科学通报·英文版

<p><b>OBJECTIVE</b>Striatum may be involved in depressive disorders according to the neuroimaging analysis and clinical data. However, no animal model at present supported the possible role of striatum in the pathogenesis of depression. In the present study, we have investigated the depressive-like behavior in mice recently intoxicated with 3-nitropropionic acid (3-NP), a widely known toxin that selectively damages the striatum in the brain.</p><p><b>METHODS</b>Mouse model was made with subacute systemic 3-NP treatment, and the depressive-like behavior was measured using the duration of immobility during forced swimming test (FST).</p><p><b>RESULTS</b>When the mice at day 15 post-intoxication just totally recovered from motor deficits, the duration of immobility in FST was significantly longer than that in controls. The depressive-like behavior was not due to the fatigue or general sickness following 3-NP intoxication and could be reversed by the antidepressant, desipramine hydrochloride. In two successive FST in 24 h interval, the depressive-like behavior could be observed again in subsequent FST (at day 16 post-intoxication), and the mice presented a normal "learned helplessness".</p><p><b>CONCLUSION</b>A novel depression animal model could be established in mice during the initial period of recovery from 3-NP intoxication. The depression-like behavior might occur independently without involvement of cognitive defects, and the striatal lesions may underlie the depression-like behavior attributable to 3-NP intoxication.</p>

Effects of preoperatively glutamine administration on rat lung injury induced by intestinal ischemia/reperfusion / 上海第二医科大学学报

Objective To evaluate effects of pretreatment with glutamine on lung injury induced by intestinal ischemia/reperfusion(II-R) in rats. Methods Glutamine or saline were injected through tail vein before the model of intestinal ischemia/reperfusion in rats were established.The gene expression of intercellular adhesion molecule-1(ICAM-1) and heat shock protein-70(HSP-70) were tested with RT-PCR methods.The levels of heat shock protein-70 in the lung were measured with Western Blotting.Myeloperoxidase and malondialdehyde and pathological changes were also measured. Results The gene expression of heat shock protein-70 was enhanced by pretreatment with glutamine,and the level of HSP-70 was parallelly increased.Nevertheless,MPO,MDA and the gene expression of ICAM-1 were inhibited. Conclusion Pretreatment with glutamine can lessen the lung injury induced by intestinal ischemia/reperfusion in rats,the induction of HSP-70 gene may be one of the potential mechanisms.

The effect of nitric oxide and total antioxide capacity on the germ cell apoptosis in the rat cryptorchid / 中华男科学杂志

<p><b>OBJECTIVES</b>To study the effect of nitric oxide (NO) and total antioxide capacity (T-AOC) on the germ cell apoptosis in the cryptorchidism rat.</p><p><b>METHODS</b>Immature rats (22 day-olds Sprague Dawley) were selected to make the model of unilateral cryptorchid. Germ cell apoptosis was examined by terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL). Biochemical parameters (NO, T-AOC) were evaluated with spectrophotometric determination.</p><p><b>RESULTS</b>At the seventh day after the operation, as compared to the normal side testis, the number of apoptotic germ cells increased significantly in the undescended testis (P < 0.01), but the testes weight decreased predominantly; the NO level in the undescended testis was significantly higher than that in the normal side testis, and the T-AOC level was predominantly lower (P < 0.01).</p><p><b>CONCLUSIONS</b>Experimentally-induced cryptorchidism can lead to the increase of grem cell apoptosis in rat. The results is closely related to the increase of No level and the decrease of T-AOC.</p>

Investigation of the mechanism of genitofemoral nerve in the contralateral testes damage of unilateral cryptorchid rats / 中华男科学杂志

<p><b>OBJECTIVES</b>To investigate the mechanism of genitofemoral nerve in the contralateral testes damage of unilateral cryptorchid rats.</p><p><b>METHODS</b>After unilateral cryptorchid rat model (21-day) was made and the ipsilateral genitofemoral nerve was divided, the germ cells apoptosis and the concentrations of lactate of contralateral testes were detected and compared after 120 days.</p><p><b>RESULTS</b>After the ipsilateral genitofemoral nerve was divided, the germ cells apoptosis and the lactate levels of the contralateral testes were all decreased from (17.28 +/- 1.36)% to (5.76 +/- 0.76)% and (2.19 +/- 0.24) mmol/L to (1.70 +/- 0.31) mmol/L, respectively.</p><p><b>CONCLUSIONS</b>The damage pathway of the contralateral testes of unilateral cryptorchidism probably related to the apoptosis of the germ cells which caused by the reflex decrease of the contralateral testicular blood flow via the transmissions of genitofemoral nerve.</p>