利拉鲁肽提高肥胖不孕多囊卵巢综合征妇女临床妊娠率的研究

目的评价利拉鲁肽与二甲双胍联合用药对减重治疗失败的多囊卵巢综合征(PCOS)不孕患者临床妊娠率及累计妊娠率的影响,同时评价联合用药对卵母细胞和胚胎质量、减重以及代谢和内分泌指数的影响。方法选取2017年6月至2018年12月间在我院治疗的186例减重失败的PCOS肥胖患者。186例患者随机分为联合用药组(联合组)与二甲双胍组,每组93例。二甲双胍组服用二甲双胍片治疗,联合组在二甲双胍组治疗的基础上,加用利拉鲁肽皮下注射治疗,初始剂量为0.6 mg,1次/d,3 d后增加至1.2 mg。所有患者均治疗12周。治疗的同时对所有患者进行积极生活方式干预,干预措施包括控制食物热量及每天进行至少30 min中等强度的身体活动,在药物治疗1个月后给予患者体外受精(IVF)手术,对患者进行12个月随访,记录患者的自然妊娠情况。比较基线期与治疗后患者的人体测量参数、内分泌参数、体脂分布参数及IVF结果。结果治疗后,联合组与二甲双胍组患者体重均较基线期显著降低(t=2.65,P<0.01;t=4.05,P<0.01)。二甲双胍组和联合组患者体重分别下降(5.98±5.03)kg和(7.52±3.90)kg。与二甲双胍组比较,联合组患者体重较基线降低值显著提高(t=2.33,P=0.02)。2组患者内脏脂肪含量、体积和面积均较基线期显著降低(P<0.05)。与二甲双胍组比较,联合组的临床妊娠率(84.0%vs.28.3%,χ^2=30.42,P<0.01)和累计妊娠率(68.8%vs.37.6%,χ^2=18.16,P<0.01)显著提高。两组患者恶心与腹泻发生率比较差异无统计学意义(χ^2=1.56,P=0.21;χ^2=0.58,P=0.45)。结论低剂量利拉鲁肽联合二甲双胍对超重不孕的PCOS患者进行短期干预,可以显著提高患者的临床妊娠率和累计妊娠率,并显著降低PCOS患者的体重、内脏脂肪组织,没有显著增加患者的药物不良反应。     

经阴道常规超声联合实时超声弹性成像评估宫颈癌同步放化疗疗效

目的 观察经阴道常规超声联合实时超声弹性成像评价宫颈癌同步放化疗（CCRT）疗效的可行性。方法 收集30例经病理确诊并接受CCRT的宫颈癌患者,于CCRT前1周（治疗前）、治疗3周（治疗中）及治疗结束1个月（治疗后）行经阴道常规超声联合实时超声弹性成像检查,于治疗前及治疗后行盆腔MRI,比较治疗前、中、后各超声参数变化。依据超声及MRI表现评估宫颈癌CCRT疗效,观察二者的一致性。结果 30例宫颈癌中,28例鳞癌、2例腺癌。治疗前、中、后病灶最大径差异均有统计学意义（P均<0.01）;治疗前、后病灶回声、血流分级、弹性评分差异均有统计学意义（P均<0.01）;治疗前、中、后病灶边界、阻力指数差异均无统计学意义（P均>0.05）。治疗后12例完全缓解、18例部分缓解,经阴道常规超声联合弹性成像评估结果与MRI结果的一致性较强（Kappa=0.72,P<0.01）。结论 经阴道常规超声联合实时超声弹性成像技术可用于评估CCRT治疗宫颈癌效果。     

Elevated antigen-specific Th2 type response is associated with the poor prognosis of hand,foot and mouth disease

The immunopathogenesis of severe hand, foot and mouth disease (HFMD) remains elusive. This study revealed that enterovirus 71 (EV71) epitope-specific CD4+ T cell responses of HFMD patients were skewed toward a Th2 cytokine profile. Patients that demonstrated higher levels of IL-4 expression in their CD4 T cells following antigen stimulation in vitro tended to have a more prolonged period of high fevers and a longer duration of illness. Thus, an increase of EV71 epitope-specific Th2 type response may portend the poor prognosis for some HFMD patients.     

Impact of tissue processing,archiving and enrichment techniques on DNA methylation yield in rectal carcinoma

Background

Formalin fixation, duration of tissue storage and tissue enrichment techniques can affect DNA methylation yield but these effects have not been quantitatively measured. The aim is to investigate the relative impact of these conditions on DNA methylation in rectal cancer.

Methods

10 rectal cancers with matched undissected fresh frozen tissues, laser capture microdissected (LCM) formalin-fixed paraffin-embedded (FFPE) tissues, manual macrodissected FFPE tissues, adjacent normal mucosa and stromal tissues were analysed for APC and LINE-1 methylation using bisulphite pyrosequencing.

Results

FFPE cancer tissues, which had been stored for at least 4 years showed similar APC and LINE-1 methylation changes to matched fresh frozen cancer tissues. Laser capture microdissection did not increase the degree of methylation detected compared to manual macrodissection. Analysis of stromal tissues showed that they had undergone significant methylation changes compared to adjacent macroscopically normal mucosa, but not to the same extent as cancer tissues.

Conclusion

Reliable DNA methylation results can be obtained from FFPE rectal cancer tissues, which have been in long-term storage. Because only minor differences in methylation between macrodissected and LCM cancer tissues were found, our results do not support the routine use of LCM to enrich for cancer cells for DNA methylation studies.     

The Effect of Osteochondral Regeneration Using Polymer Constructs and Continuous Passive Motion Therapy in the Lower Weight-Bearing Zone of Femoral Trocheal Groove in Rabbits

Remedying patellofemoral osteochondral defects using clinical therapy remains challenging. Construct-based and cell-based regenerative medicine with in vitro physical stimuli has been progressively implemented. However, the effect of physical stimuli in situ in knee joints with degradable constructs is still not well-documented. Therefore, we studied whether it was practical to achieve articular cartilage repair using a poly(lactic-co-glycolic acid) (PLGA) construct in addition to early short-term continuous passive motion (CPM) for treatment of full-thickness osteochondral defects in the lower-weigh bearing (LWB) zone of the femoral trocheal groove. Twenty-six rabbits were randomly allocated into either intermittent active motion (IAM) or CPM treatment groups with or without PLGA constructs, termed PLGA construct-implanted (PCI) and empty defect knee models, respectively. Gross observation, histology, inflammatory cells, which were identified using H&E staining, total collagen and alignment, studied qualitatively using Masson’s trichrome staining, glycosaminoglycan (GAG), identified using Alcian blue staining, and newly formed bone, observed using micro-CT, were evaluated at 4 and 12 weeks after surgery. Repair of osteochondral defects in the PCI-CPM group was more promising than all other groups. The better osteochondral defect repair in the PCI-CPM group corresponded to smooth cartilage surfaces, no inflammatory reaction, hyaline cartilaginous tissues composition, sound collagen alignment with positive collagen type II expression, higher GAG content, mature bone regeneration with osteocyte, clear tidemark formation, and better degradation of PLGA. In summary, the use of a simple PLGA construct coupled with passive motion promotes positive healing and may be a promising clinical intervention for osteochondral regeneration in LWB defects.     

Attachment,affective temperament,and personality disorders: A study of their relationships in psychiatric outpatients

Background

As the result of extensive translational and cross-disciplinary research, attachment theory is now a construct with significant neuropsychiatric traction. The correlation of attachment with other influential conceptual models (i.e. temperament and personality) is therefore of interest. Consequently, we explored how two attachment dimensions (attachment anxiety and attachment avoidance) correlated with measures of temperament and personality in 357 psychiatric outpatients.

Methods

We performed a retrospective review of four questionnaires (the Experiences in Close Relationship scale (ECR-R), Temperament and Character inventory (TCI), Temperament Evaluation of the Memphis, Pisa, Paris and San Diego questionnaire (TEMPS-A), and Personality Self-Portrait Questionnaire (PSQ)). Frequency measures and correlations were examined, as was the predictive value of attachment security for a personality disorder (PD).

Results

Significant, robust correlations were found between attachment anxiety and (1) several negative affective temperaments (dysthymic and cyclothymic); (2) several indices of personality pathology (low self-directedness (TCI), DSM-IV paranoid, borderline, histrionic, avoidant and dependent personality traits). Attachment avoidance had fewer large correlations. In an exploratory model, the negative predictive value of attachment security for a PD was 86%.

Limitations

Subjects were a relatively homogeneous subset of ambulatory psychiatric outpatients. PD diagnoses were via self-report.

Conclusions

Clinically, these findings highlight the significant overlap between attachment, affective temperament, and personality and support the value of attachment as a screen for PDs. More broadly, given our growing understanding of the neurobiology of attachment (i.e. links with the oxytocin system), these results raise interesting questions about underlying biological systems and psychiatric treatment.     

Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B

The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg.