Over-expression of suppressor of cytokine signaling 3 inhibits the proliferation of human mesangial cells stimulated by aggregated IgA1 from IgA nephropathy patients / 中华肾脏病杂志

Objective To investigate the effect of suppressor of cytokine signaling 3 (SOCS3)on the proliferation of human mesangial cells stimulated by aggregated IgA1 (aIgA1) from patients with IgA nephropathy(IgAN),and explore its possible mechanism.Methods Serum monomeric IgA1 was isolated with jacalin affinity and Sephacryl S-200 HR chromatography from IgAN patients,and then heated to aggregated form (aIgA1).Human glomerular mesangial cells(HMC) were transfected with AdvSOCS3-IRES2-EGFP for 48 hours,and incubated with aIgA1 for 12-48 h.The cells were divided into blank control group,IgA1 group,IgA1 +Adv-EGFP group and IgA 1 +Adv-SOCS3-IRES2-EGFP group.The mesangial cell proliferation was observed through MTT,and the levels of SOCS3,TLR4,TGF-β1 protein and mRNA were detected through Western blotting and real-time PCR.Results HMC proliferation was promoted significantly after IgA1 stimulated at 24 h.Compared with control group,the protein and mRNA expression of SOCS3,TLR4,TGF-β1 were significantly increased in IgA1 group (P ＜ 0.05).Compared with IgA1 group and IgA1 +Adv-EGFP group,MTT absorbency was obviously reduced after incubation with aIgA1 for 24 h and 48 h in IgA+Adv-SOCS3-IRES2-EGFP group,and the protein and mRNA expression of TLR4 and TGF-β1 were significantly decreased in IgA1 +AdvSOCS3-EGFP group (P＜ 0.05).Conclusion Over-expression of SOCS3 may inhibit the proliferation of HMC stimulated by aIgA1,partly through down-regulating the expression of TLR4 and TGF-β1.

Angiotensin Ⅱ up-regulates the release of inflammation factors via Toll-like receptor 4 signal in rat mesangial cells under high glucose / 中华肾脏病杂志

Objective To observe the regulation of Toll-like receptor 4 (TLR4) signal and the release of inflammation factors after angiotensin Ⅱ (Ang Ⅱ) stimulation in rat mesangial cells under high glucose condition,revealing the innate immune-related mechanism of injury by Ang Ⅱ on mesangial cells under high glucose.Methods After synchronization,cells incubated with Ang Ⅱ (10-7 mmo/L) and/or high glucose (25 mmol/L) were used as the stimulation group,cells without stimulation were as normal control (5.6 mmol/L glucose).To determine the role of TLR4 and the adaptor myeloid differentiation factor 88 (MyD88),equal number of HBZY-1 cells were added with 10-5 mmol/L irbesartan and/or TLR4 blocker (10 mg/L) for 1 h and then incubated with Ang Ⅱ (10-7 mmo/L) and/or high glucose (25 mmol/L) for 12 h or 24 h respectively.Real-time PCR was used to analyze TLR4 mRNA and MyD88 mRNA expression after 12 h.Immunofluorescence was used to observe TLR4 protein expression after 24 h; Western blotting was used to observe TLR4,MyD88 and nuclear factor κB (NF-κB) protein; ELISA was used to detect the concentration of MCP-1,IL-6 in cell supernatant respectively.Results Compared with normal control group,TLR4 mRNA and MyD88 mRNA were highly expressed in high glucose or Ang Ⅱ-induced HBZY-1 cells (P ＜ 0.01),TLR4,MyD88 and NF-κB protein as well as MCP-1,IL-6 were also up-regulated significantly (P ＜ 0.01).Compared with high glucose or Ang Ⅱ group,MyD88 and NF-κB protein as well as MCP-1,IL-6 were further up-regulated markedly in Ang Ⅱ and high glucose costimulated group (P ＜ 0.01).In HBZY-1 cells that were preincubated with irbesartan and/or TLR4 blocker,TLR4 and MyD88 protein expression were obviously inhibited,IL-6 and MCP-1 production were also decreased remarkably compared with high glucose and/or Ang Ⅱ group (P ＜ 0.01).Conclusions High glucose and Ang Ⅱ stimulate the release of proinflammatory factors in rat glomerular mesangial cells via TLR4-MyD88 pathway.This process is inhibited by irbesartan or TLR4 blocker via modulation of the signal.Ang Ⅱ has the positive-regulation potential on the release of inflammation factors via TLR4 signal in rat mesangial cells under high glucose condition.

Clinical features of thyrotoxic periodic paralysis caused by inwardly rectifying potassium channel 18 gene mutations / 中华神经科杂志

Objective To report the clinical features and inwardly rectifying potassium channel 18 (KCNJ18) gene mutation in a group of patients with thyrotoxic periodic paralysis (TTP).Methods Fiftyseven TTP cases (55 male and 2 female) were collected in our clinic from July 2002 to October 2011.The KCNJ18 gene was directly sequenced in 57 TTP patients and 50 health Chinese controls through the nested PCR.According to the results of gene screening,the clinical features of KCNJ18 patients and non-KCNJ18 patients were retrospectively summarized and analyzed.Results In 4 male patients with TPP,we found 3 novel heterogeneous mutations (p.Q126X,p.K360T,p.E388K) and 1 reported mutation (p.A200P) in the KCNJ18 gene.The age of onset was 19-25 years old,and the duration ranged from 2 to 8 hours.The 4 patients all presented severe muscle weakness.The attacks of muscle weakness preceded overt symptoms of hyperthyroidism in the 4 patients. Three patients showed recurrent weakness during the 13-28 months follow-up,while the episodic weakness never appeared when patients got euthyroid. Conclusions The mutations in the KCNJ18 gene are responsible for a part of Chinese patients with TPP.The patients with KCNJ18 mutations have a shorter disease course,severer manifestation,and higher prevalence of recurrence as compared with those TPP patients without KCNJ18 mutations.

Characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence detected by transperineal three-dimensional ultrasound / 中华妇产科杂志

Objective To identify the morphological characteristics of pelvic diaphragm hiatus in pregnant women with stress urinary incontinence ( SUI) by transperineal three-dimensional (3-D) ultrasound.Methods From Oct.2008 to Mar.2009,145 pregnant women (third trimester group) at 37-41 weeks of gestation underwent transperineal 3-D ultrasound investigation at Department of Obstetrics and Gynecology,the Sixth People's Hospital,Shanghai Jiaotong University,including 38 pregnant women with stress urinary incontinence (SUI) and the other 107 non SUI pregnant women.In the mean time,50 normal nulliparous healthy women were chosen as control group.The morphological characteristics of pelvic diaphragm hiatus,the diameter of pelvic diaphragm hiatus,pubovisceral muscle thickness and genitohiatal and levator ani angle were measured at rest,on maximum Valsalva and maximum pelvic floor contraction by 3-D ultrasound,respectively.Results Loosen connective tissue and pubococcygeus avulsion were observed in some pregnant women at third trimester.The area of pelvic diaphragm hiatus were (15.2 ±1.9),(16.4 ± 2.0) and (13.6±1.9) cm2,pubovisceral muscle thickness were (0.72 ±0.11),(0.68 ±0.14) and(0.77 ±0.11) cm,levator ani angle were (60 ±8) °,(57±10) ° and (64 ± 14)° at rest,on maximum Valsalva and maximum pelvic floor contraction respectively.These parameters were significantly increased than those in control group[(11.2 ±2.6),(14.5 ±4.5) and (9.2 ±2.6) cm2; (0.66 ±0.10),(0.67 ± 0.14) and (0.71 ±0.14) cm; (50 ±4) °,(51 ±5) ° and (46 ±5)°]at three maneuvers,respectively ( P <0.05).And those parameters of the anteroposterior hiatal diameter,lateral hiatal diameter,perimeter of pelvic diaphragm hiatus and area of pelvic diaphragm hiatus in SUI pregnant women were increased than those in non SUI pregnant women at three maneuvers,respectively (P < 0.05 ).Pubovisceral muscle thickness in SUI pregnant women was significantly lower than that in non SUI pregnant women at maximum pelvic floor contraction (P < 0.05 ),but there were not significant difference between SUI and non SUI pregnant women at rest and on maximum Valsalva in pubovisceral muscle thickness and genitohiatal and levator ani angle (P >0.05).Conclusions Pelvic floor anatomic remodeling is identified in late pregnant women.When compared with non pregnant women,the loosen pelvic floor connective tissue and the bigger diameters of pelvic diaphragm are observed in late pregnant women.It is observed that the increased diameters of pelvic diaphragm and decreased thickness of pubovisceral muscle in later pregnant SUI women than those in non SUI pregnant women.

Relationship between pelvic floor dysfunction and serum relaxin H2 and expression of vaginal wall relaxin receptor LGR7 mRBA in late pregnant women / 上海交通大学学报（医学版）

Objective To investigate the relationship between pelvic floor dysfunction and serum relaxin H2 and expression of vaginal wall relaxin receptor LGR7 mRNA in late pregnant women. Methods Before the beginning of delivery,all women were evaluated by pelvic organ prolapse quantitation(POP-Q)scoring.Twelve women with stress urinary incontinence(SUI)and stage II prolapse of anterior vaginal wall were selected as patient group,and another 24 women without SUI and prolapse of pelvic floor were served as control group.Serum relaxin H2 was determined by ELISA.Vaginal wall tissues were taken after vaginal delivery,and the expression of relaxin receptor LGR7 mRNA was detected by RT-PCR.Results The serum level of relaxin H2 and expression of LGR7 mRNA of vaginal tissues in patient group were significantly higher than those in control group(P<0.01,P<0.05). Conclusion The increased level of serum relaxin and expression of vaginal wall relaxin receptor may correlate with the pelvic floor dysfunction in late pregnant women.

A prospective study of postpartum depression: biological and psychosocial factors / 中国神经精神疾病杂志

Objective 　The study aimed to measure the prevalence of postpartum depression, as well as their relevant psychosocial and biological factors. Methods　A sample of 299 women were prospectively studied at 3 day postpartum and 117 were reassessed at 42 day postpartum. They completed EPDS, some self-designed demographic and psychological investigation questionnaires. Results　23.08% suffered from postpartum depression. Some psychosocial factors such as support system were signigicantly related to the postnatal depression. Conclusions　Postpartum depression has social and psychological causal factors.