Erythropoietin (EPO) belongs to cytokines.It mainly promotes erythropoiesis in the peripheral blood circulation.Fundamental research shows that EPO can reduce cerebral ischemic injury through a variety of mechanisms,but at the same time,there are many unsolved problems.In addition,the two clinical trial outcomes are also very inconsistent.This article reviews the problems in EPO research.

Objective To study the mental status and its influencing factors of patients with rheumatic disease. Methods Three hundreds and eighty-one patients with rheumatic diseases were assessed with the self-rating anxiety scale, self-rating depressive scale, Eysenck Personality Questionnaire symptom checklist-90, and demographic characteristics questionnaire. The comparison among groups were tested by t tests, Spearman's correlation analysis. Results Patients with anxiety symptoms accounted for 35.96%, and pre-valence rate of depression was 48.03%. The gender (r=0.87, OR=2.34) and duration (r=0.006, OR=1.006) were the risk factors and the C4 (r=-2.63, OR=0.07) was the protective factor. In patients with systemic lupus erythematosus, depression was related to education (Z=2.228, P=0.026), disease duration (Z=-2.015,P=0.044), IgG level (t=-2.266, P=0.027), T cell subsets CD8 (Z=1.981, P=0.047) and CD3 (Z=1.967, P=0.049). Anxiety was related to education (Z=2.452, P=0.014), duration (Z=-2.054, P=0.04), complement C3 (t=2.035, P=0.045), C4 (Z=-2.204, P=0.028) and IgG level (t=-2.126, P=0.036). The value of CRP(Z=-1.984, P=0.047) and IgM (t=2.243, P=0.028) of rheumatoid arthritis patients were higher in the depression group. The depression group was different in disease duration (Z=-2.631, P=0.009), gender ( χ2=4.415, P=0.042), ESR (Z=2.17, P=0.023) and CD3 cell (Z=2.023, P=0.043) in Sj?gren's syndrome patients. Correlation analysis showed positive correlation between the score of SDS, SAS and the P value (r=0.21, P=0.01) (r=0.14, P=0.007) N dimension (r=0.52, P=0.01) (r=0.55, P=0.007) of EPQ. There were negative correlation between the score of SDS, SAS and the E dimension (r=-0.23, P=0.01) (r=-0.14, P=0.006) of EPQ. Conclusion The prevalence of depres-sion and anxiety is higher in patients with depressive and anxious symptoms. They are in older age, female gender, poor education, longer duration, lower complement and lower T cell subsets when compared with those patients without depression and anxiety. Patients who have an introverted, instable, nervous temperament are more likely to be depressed and anxious. Psychological assessment intervention and therapy should be carried out as early as possible.

Objectives To observe the effect of Luoyutong capsule on neurological function following focal cerebral ischemia-reperfusion in rats and to preliminarily study the protective mechanism of Luoyutong capsule for focal cerebral ischemia-reperfusion in rats. Methods A rat model of middle cerebral artery occlusion (MCAO)was induced by the modified Longa method. After 1. 5 h of ischemia,reperfusion started. Ten male SD rats were selected as sham operation group,and forty male SD rats were randomly divided into 4 groups:Model (MCAO),Luoyutong moderate-dose (LYTM),Luoyutong high-dose (LYTH),and citicoline sodium (CS)groups (n=10 in each group). At day 3 and 7 after modeling,the neurological function of the rats was evaluated by using 12 neurological score and forelimb placing test. Western blotting was used to detect the expression levels of brain derived neurotrophic factor (BDNF),basic fibroblast growth factor (b-FGF),and phosphor/protein kinase (p-AKT/AKT)on the ischemic side of the rats and in the ipsilateral brain tissue at day 3 after modeling,as well as the expression level of Caspase-12 at day 7 after modeling in the ipsilateral brain tissue,and a comparison was performed among the groups. Results (1 )Neurological score:At day 3 after modeling,there was no significant difference between the 12 neurological score and the forelimb placing test score (all P>0. 05);At day 7 after modeling, there were obvious improvement in the LYTM,LYTH,and CS groups compared with model group (all P<0.05). (2)The results of western blot showed that①compare with the sham operation group,the expression levels of BDNF and b-FGF were reduced obviously (all P<0.05);compare with the MCAO group,the expression levels of the LYTM,LYTH and CS groups could be up-regulated,particularly in the LYTH group (P<0. 01);② compare with the sham operation group,the expression level of p-AKT/AKT in MCAO group was decreased obviously (P<0. 05);compare with the MCAO group,the expression levels of p-AKT/AKT of the LYTM,LYTH,and CS groups were increased,particularly in the LYTH and CS groups (all P<0. 05);③ compared with the sham operation group,the expression of cleavage Caspase-12 was increased obviously in the MCAO group (P<0. 05). Compared with the MCAO group,the expression levels of proCaspase-12 and cleavage Caspase-12 had a decreasing trend in the LYTM and LYTH groups,but there were no significant differences (all P >0. 05);the expression levels of proCaspase-12 and cleavage Caspase-12 in the CS group were obviously lower than those of the MCAO group (P<0. 05). Conclusion Luoyutong capsule may play a protective effect for focal cerebral ischemia-reperfusion injury in rats by promoting neural survival and regeneration,and this protective effect may be associated with the inhibition of neuronal apoptosis.

Objective To compare the curative effect and biomechanical performance of cannulated compression screw (CCS) and dynamic hip screw-blade (DHS-B) in the treatment of patients with femoral neck fracture.Methods Between February 2010 and February 2014,102 patients with femoral neck fracture were treated with CCS or DHS-B at our department.They were 54 males and 48 females,aged from 15 to 86 years.There were 30 subcapital fractures,51 transcervical ones and 21 base ones.CCS was used in 60 patients and DHS-B in 42.In-hospital data were collected retrospectively to compare the curative effects in 2 groups.Furthermore,femoral neck fracture models were established using 12 adult cadaveric femoral specimens.The 12 models were randomized into 2 equal groups (n =6).Group A was subjected to fixation by 3 CCSs and group B to fixation by DHS-B.The 2 groups were compared in terms of axial loading test,rotation test and destructive axial loading test.Results The operation time (59.4 ± 20.2 min),incision size (4.1 ±0.6 cm) and intraoperative blood loss (25.9 ±9.9 mL) in the CCS group were significantly less than those in the DHS-B group (88.6±22.9 min,12.1 ±1.2cmand 156.7±107.1 mL) (P ＜0.05).The Harris hip score for the DHS-B group (91.9±9.8) was significantly higher than that for the CCS group (87.2 ± 9.2) (P ＜ 0.05).There were no significant differences between the 2 groups in hospital stay,partial weight-bearing time,or postoperative complications (P ＞ 0.05).At 500 N vertical loading,the stress values at both medial and lateral sides of the femur in group A were significantly smaller than those in group B (P ＜ 0.05).There were no significant differences between groups A and B in the average sinking displacement of femoral head or the torque at a torsion angle of 6° (P ＞ 0.05).The maximum load in group A (2,135 ±120 N) was significantly smaller than that in group B (2,986 ± 98 N) (P ＜ 0.05).Conclusion In treatment of femoral neck fracture,DHS-B fixation is obviously superior to CCS fixation,because the former is in better agreement with the femoral biomechanical property,and performs better in anti-rotation and anti-compression,leading to better functional recovery of the affected hip.

Objective:To investigate the clinical features and influencing factors of renal artery involvement in patients with Takayasu's arteritis (TA).Methods:One hundred and five TA patients were included and their clinical features, laboratory tests, echocardiographic findings were collected and analyzed. The t-test, Mann-Whitney U test, Sperman's correlation and logistic regression were used for statistical analysis. Results:Of the 105 patients with Takayasu's arteritis, 21 (20%) patients were diagnosed to have renal artery involvement. They had higher frequency of hypertension [76%(16/21) vs 25%(21/84); χ2=19.291, P<0.01], syncope [19%(4/21) vs 4%(3/84); P=0.028] and headache [52%(11/21) vs 25%(21/84); χ2=5.944, P=0.019]. Patients with renal artery invol-vement had higher levels of creatinine [(67±30) mmol/L vs (50±14) mmol/L; t=2.436, P=0.023], lower levels of lymphocyte subsets CD3 +[1 299(1 261.5, 1 313.45)/μl vs 1 531 (1 330, 1 559.5)/μl; Z=-3.12, P=0.002], CD4 +[793.6(715, 804.32)/μl vs 914.88(794.3, 914.8)/μl; Z=-2.597, P=0.009], CD8 +[451.09(451.09, 489.5)/μl vs 552.39(459.75, 557.5)/μl; Z=-3.271, P=0.001] and glomerular filtration rate ( Z=-2.612, P=0.009). Comparison of echocardiographic parameters between the two groups showed that the diameters of left atrium [(35±4) mm vs (32±4) mm; t=3.065, P=0.003] and end-diastolic left ventricular [49.2(47.5, 52.5) vs 45.84(43.25, 47.75); Z=-3.795, P<0.01] were larger in renal artery involvement group. Abdominal aorta ( χ2=14.292, P<0.01), superior mesenteric artery ( P<0.01), inferior mesenteric artery ( P=0.038) and common iliac artery ( P=0.005), were more likely involved in patients with renal artery involvement; while the common carotid artery ( χ2=3.815, P=0.047) and subclavian artery ( P=0.022) were less affected. There was a positive correlation between creati-nine level ( r=0.282, P=0.004) and renal artery involvement in patients with arteritis, and the number of lymphocyte subsets (CD3, CD4, CD8) ( r=-0.306, P=0.002; r=-0.255, P=0.009; r=-0.321, P=0.001) was negatively correlated with renal artery involvement. Conclusion:The most common pattern of renal artery involvement is stenosis and occlusion. Hypertension, syncope, headache, kidney dysfunction and heart failure are more prevalent among patients with renal artery involvement. The number of lymphocyte subsets is low, and involvement of abdominal aorta is common. It should be assessed and treated as soon as it is discovered.

Objective:To explore the relationship between the expression of p57KIP2,cyclin D1,and cyclin E receptors in male breast can-cer(MBC)and its clinical significance.Methods:Data of MBC cases diagnosed in The First Affiliated Hospital of Wenzhou Medical Uni-versity between January 2000 and December 2016 were reviewed.Forty cases of infiltrating ductal carcinoma(IDC)and 20 cases of male ductal carcinoma in situ(DCIS)were selected,and 20 cases of gynecomastia(GYM)were selected as controls.The expression of p57KIP2,cyclin D1,and cyclin E mRNA and protein in the tissue samples obtained from IDC,DCIS,and GYM cases were measured by re-verse transcription polymerase chain reaction and immunohistochemistry,respectively.Results:The expression of p57KIP2mRNA in IDC was 0.18±0.07,which was lower than that in DCIS(0.42±0.05)and GYM(0.75±0.04).The rate of p57KIP2positivity in IDC was 25%(10/40),which was lower than that in DCIS 60%(12/20)and GYM 90%(18/20).There were significant differences in the expression of p57KIP2mRNA and protein among the three groups(P<0.05).The expression of cyclin D1 and cyclin E mRNA in IDC was 0.92±0.12 and 0.96±0.08,which was higher than that in DCIS(0.72±0.06,0.64±0.01)and GYM(0.38±0.03,0.21±0.02),respectively.Cyclin D1 and cy-clin E protein positive rates in IDC were 90%(36/40)and 88%(35/40),which were higher than those in DCIS[80%(16/20),85%(17/20)],and GYM[25%(5/20),20%(4/20)].In IDC tissues,the expression of p57KIP2,cyclin D1,and cyclin E proteins was associated with the clinical stage and histological grade(P<0.05),and the expression of p57KIP2protein was correlated with axillary node metastasis(P<0.05).There was a negative correlation between the expression of p57KIP2and cyclin D1 and between p57KIP2and cyclin E.However,the correlation between cyclin D1 and cyclin E expression was positive(P<0.05).Conclusions:p57KIP2,cyclin D1,and cyclin E may play an im-portant role in the development and progression of MBC.Combined clinicopathological detection of p57KIP2,cyclin D1,and cyclin E can aid future research on MBC.

Objective To observe the effects of electroacupuncture at"Ciliao","Zhongji","Sanyinjiao"and"Dazhui"on urodynamics and expression of ERK/CREB/Bcl-2 pathway in spinal cord tissue of neurogenic bladder rats after suprasacral spinal cord injury.Methods Sixty female SD rats randomly selected 24 and divided into blank group and sham-operation group(12 rats in each group),the remaining 36 rats were subjected to surgical modeling.After modeling,rats were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.The electroacupuncture group received unilateral electroacupuncture stimulation at acupoints"Ciliao","Zhongji","Sanyinjiao",and"Dazhui"for 30 minutes each time,once a day,for 7 consecutive days.After administration,urodynamic testing was performed,HE staining was used to observe the morphology of bladder detrusor tissue,TUNEL method was used to detected apoptosis in spinal cord tissue,Western blot was used to detected expressions of p-ERK1/2,p-CREB,p-p90Rsk,CRE,Bcl-2,and Bax proteins in spinal cord tissue.Results Compared with the sham-operation group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the model group increased significantly(P<0.01),while the maximum capacity and compliance of the bladder decreased significantly(P<0.01);the structure of bladder smooth muscle cells was severely damaged and disorderly arranged,accompanied by a large amount of inflammatory cell infiltration;the apoptosis rate of spinal cord tissue cells significantly increased(P<0.01),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue were significantly decreased,while the expression of Bax protein significantly increased(P<0.01).Compared with the model group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the electroacupuncture group decreased significantly(P<0.05),while the maximum capacity and compliance of the bladder increased significantly(P<0.05,P<0.01);the integrity of bladder smooth muscle cells was enhanced,the degree of cell edema was reduced,and inflammatory cell infiltration was reduced;the apoptosis rate of spinal cord tissue cells was significantly reduced(P<0.05),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue significantly increased,while the expression of Bax protein was significantly decreased(P<0.05,P<0.01).Conclusion Electroacupuncture can promote the repair of bladder detrusor tissue in rats with neurogenic bladder model after suprasacral spinal cord injury,increase the maximum capacity and compliance of the bladder,alleviate the high pressure state in the bladder,and its mechanism is related to activating the ERK/CREB/Bcl-2 pathway,reducing secondary apoptosis of damaged neurons,effectively improving bladder innervation,and protecting bladder function.

OBJECTIVE: To summarize the genetic characteristics of 671 Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD). METHODS: Clinical data of the pedigrees were collected. Multiplex PCR, multiple ligation dependent probe amplification (MLPA), next generation sequencing (NGS), Sanger sequencing and long read sequencing were used to detect the variant of DMD gene in the probands and their mothers, and prenatal diagnosis was provided for high risk pregnant women. RESULTS: Among 178 pedigrees analyzed by multiplex PCR, 44 variants of the DMD gene were detected, with the genetic diagnosis attained in 110 pedigrees. Among 493 pedigrees analyzed by MLPA in combination with NGS or Sanger sequencing, 294 pathogenic/possible pathogenic variants were identified, among which 45 were unreported previously, and the genetic diagnosis attained in 484 pedigrees. Structural variants of the DMD gene were identified in two pedigrees by long-read sequencing. Among 444 probands, 341 have inherited the DMD gene variant from their mothers (76.8%). Among 390 women with a high-risk, 339 have opted to have natural pregnancy and 51 chose preimplantation genetic testing for monogenetic disease (PGT-M). The detection rate of neonatal patients and carriers following natural pregnancy was significantly higher than that for PGT-M. CONCLUSION Combined application of MLPA, NGS, Sanger sequencing and long-read sequencing is an effective strategy to detect DMD/BMD. PGT-M can effectively reduce the risk of fetuses. Above finding has expanded the spectrum of DMD gene variants and provided a basis for reproductive intervention for pregnancies with a high risk for DMD/BMD.
China ; Dystrophin/genetics* ; Exons ; Female ; Genetic Testing ; Humans ; Infant, Newborn ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophy, Duchenne/genetics* ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

Objective Colon-targeting capsules based on gastric pellets and enteric pellets were prepared from Baizhu Huanglian prescription. The formulation composition and preparation process were optimized and the in-vitro release characteristics were investigated. Methods Optimum formulation composition and process parameters of Baizhu Huanglian pellets were screened out by single factor experiment and orthogonal design. The pellets core were prepared by extrusion-spheronization technique and coated in the fluid bed using bottom spray coating technique. To investigate the effect of coating level of the isolation layer, the proportion of polymer, the amount of plasticizer and weight gain of enteric coating on the release behavior of the enteric pellets. The pellets release behavior was fitted by model as well. Results The prescription of gastric pellets was drug loading 50%, PVPP 5%, MCC to lactose 1∶2 and wetting agent 40%. The process parameters were extrusion frequency 20 Hz, rounding speed 500 r/min and rounding time 5 min. The prescription of enteric pellets was drug loading 27%, PVPP 5%, MCC to lactose 5∶2, wetting agent 30% and adhesive 20%. The process parameters were extrusion frequency 20 Hz, rounding speed 700 r/min and rounding time 7 min. For enteric coating layer, the coating mixture of EUDRAGIT®L30D-55 to EUDRAGIT® FS30D was 1∶2. The amount of plasticizer was 10%. The increased weight of coating layer was 15%. The release time of enteric pellets in-vitro was up to 24 hours. The release behavior of the pellets conforms to the Higuchi model. Conclusion The colon targeting capsule of Baizhu Huanglian pellets were successfully prepared and showed the characteristics of sustained release and colon targeting.