Objective To explore the change rule and clinical application value of hemorheologic indexes in patients with acute intracerebral hemorrhage ( ICH) . Methods The hemorheology indexes of 100 acute ICH patients ( ICH group) were detected within 24 h, and compared with 30 normal controls ( normal control group) . The effect of hemorheology index on history of hypertension, hemorrhage quantity and the hemorrhage location were analyzed. Results Compared with those in normal control group, the indexes of whole blood viscosity, plasma viscosity and erythrocyte sedimentation rate were significantly increased and erythrocyte aggregation index, erythrocyte deformability index and hematocrit were significantly decreased in acute stage ( all P< 0. 01 ) . Blood rheology indexes were changed significantly in hypertensive cerebral hemorrhage group (all P<0. 01), the whole blood viscosity (200 s-1 and 50 s-1 ) , erythrocyte aggregation index, hematocrit and erythrocyte sedimentation rate in non-hypertensive cerebral hemorrhage group were changed significantly ( P< 0. 05 - 0. 01 ). Compared with normal the non-hypertensive cerebral hemorrhage group, the whole blood rheology indexes except erythroate sedicmnt ation rate significantly erythrocyte sedimentation rate were significantly changed ( P< 0. 05 ) . As the hemorrhage quantity increased in each groups, the whole blood viscosity ( 200 s-1 and 50 s-1 ) and plasma viscosity of cerebral hemorrhage patients were significantly increased, otherwise the erythrocyte aggregation index was significantly decreased (P<0. 05-0. 01). There were statistical differences compared the indexes of whole blood viscosity (200 s-1 and 1 s-1 ) , plasma viscosity, erythrocyte aggregation index and erythrocyte sedimentation rate among each groups of different hemorrhage locations in acute ICH patients (all P<0. 05). Conclusions The blood of acute ICH patients shows a state of concentrated, sticky, aggregation and coagulation that severely affects the prognosis. The patients with hypertension and greater hematoma changed obviously, different hemorrhage location affected differently.

OBJECTIVE:To provide reference for the sustainable development of pharmaceutical enterprises in Guizhou prov-ince. METHODS:A questionnaire was conducted for 55 pharmaceutical enterprises in Guizhou province,the basic situation of en-terprises,familiarity of related directors to Good Manufacture Practice of Drugs(GMP)and relevant policy,the current situation of implementing the new version GMP were investigated and statistically analyzed,problems were found,and corresponding coun-termeasures were put forward. RESULTS & CONCLUSIONS:Totally 55 questionnaires were sent out,49 valid ones were received with effectively recovery of 85.1%. The results showed 43 enterprises(87.8%)had passed the GMP authentication;only 13 enter-prises(26.5%)directors were very familiar with the new version GMP. In terms of personnel management,the head of production management and quality management and the authorized person of quality and personnel had not yet met related requirements of the new version GMP fully;in terms of equipment and production management,production area transformation(clean areas,lounges, warehouses,water use) and air purification system design in most enterprises met related requirements of the new version GMP, 23 enterprises (46.9%) still can not conduct fully inspection to products and materials;in terms of document management,there were still some enterprises not meeting the new version GMP standards fully,enterprises'documents(health area layout,air purifi-cation layout,management procedures,operating procedures,etc.) of production site were imperfect. According to the investiga-tion,the main existing problems included lack of funds in implementing the new version GMP reform,not enough understanding or familiarity with the new version GMP,relevant personnel management not reaching the designated position,equipment and pro-duction management needing to be strengthened,document management systemic being poor,risk management being not sound, etc. It is suggested that government should give all forms of capital policy and strengthen the training of the new version GMP;en-terprises should attach great importance to the relevant personnel management,strengthen the equipment and production manage-ment,set up perfect document management system and a sound system of risk management.

Objective To investigate and evaluate the correlation between brain natriuretic peptide (BNP) and gestational hypertension and preeclampsia of hypertensive disorder complicating pregnancy (HDCP).Methods Fifty cases with HDCP and 46 cases with mild and 83 cases with sever stage preeclampsia were selected as our subjects.And 33 cases with regular pregnancy and 31 with irregular pregnancy were served as control group.Plasma brain natriuretic peptide,urinary protein quantity(UBQ),24-hour urinary protein assay (UPA) were measured.The correlations of brain natriuretic peptide and UBQ,UPA,systolic pressure (SP),diastolic pressure (DP) were analyzed.Results The levels of brain natriuretic peptide in the group with gestational hypertension and mild,severe preeclampsia groups were (48.54± 18.27),(79.46± 32.18) and (292.24±213.08) ng/L,higher than that in normal pregnancy and non pregnant group ((27.84± 14.58) and (20.63± 8.28) n/L;F =49.583,P＜0.05).While no significant difference exists between normal pregnancy group and non pregnant group.Grouped on the median values (199) of brain natriuretic peptide of the severe preeclampsia group,the levels of 24-hour UPA,systolic pressure and diastolic pressure were (5.46±2.68) g,(174.55± 13.58) mmHg,(113.74±9.91) mmHg in patients with brain natriuretic peptide ≥ 199 ng/L(n=42),significant higher than those in patients with brain natriuretic peptide ＜ 199 ng/L(n =41;(4.34± 1.95)g,(165.31±11.12) mmHg,(106.05±8.02) mmHg;t=2.603,3.396,2.308;P=＞0.010,0.001,0.024).The levels of 24-hour UPA,systolic pressure and diastolic pressure of patients with brain natriuretic peptide ≥ 86ng/L(n=20) in mild preeclampsia were (1.68±0.27) g,(163.69±8.29) mmHg,(105.45±6.71) mmHg,significant higher than those in patients with brain natriuretic peptide ＜ 86 ng/L (n =26;(1.16 ± 0.31) g,(152.90±7.32) mmHg,(99.19 ± 5.25) mmHg;t =3.180,2.508,2.32;P =0.010,0.016,0.025).Brain natriuretic peptide was closely correlated with UPA,systolic pressure and diastolic pressure in hypertensive disorder complicating pregnancy (HDCP) (r =0.29,0.30;P ＜ 0.01).Brain natriuretic peptide was closely correlated with UPA systolic pressure and diastolic pressure in mild preeclampsia (r =0.39,0.37,0.40;P ＜0.01).And correlation efficacy of brain natriuretic peptide with UPA,systolic pressure and diastolic pressure were 0.44,0.42 and 0.53 (P＜0.01).Conclusion The level of brain natriuretic peptide is closely associated with the severity of gestational hypertension and preeclampsia of hypertensive disorder complicating pregnancy.Correlation of brain natriuretic peptide to the severity of gestational hypertension and preeclampsia is independent of urinary protein and hypertension.Brain natriuretic peptide is an important indicator for the severity of gestational hypertension and preeclampsia of hypertensive disorder complicating pregnancy.

Objective To investigate the expressions of Toll-like receptor (TLR)-1,TLR-3,TLR-9 in peripheral blood mononuclear cells (PBMC) of children with idiopathic nephrotic syndrome (INS).Methods The expressions of TLR-1,TLR-3 and TLR-9 mRNA were measured by real time-polymerase chain reaction (RT-PCR) in PBMC of 45 children with INS came from the First Affiliated Hospital of Xinxiang Medical University before and after treatment (active group and remission group,respectively) and 30 healthy children from medical examination center as healthy control group,so as to explore the relativity between TLR-1,TLR-3 and TLR-9 mRNA and serum levels of albumin and cholesterol.Results The expression of TLR-1 mRNA/β-actin in PBMC of children with INS before treatment (the active group) was significantly higher than that in the remission group (2.432 ± 0.231 vs.1.675 ± 0.627,t =7.599,P ＜ 0.05) and the healthy control group (2.432 ± 0.231 vs.0.512 ± 0.228,t =35.446,P ＜0.05),and the differences were statistically significant in the expression of TLR-1 mRNA/β-actin between remission group and healthy control group (1.675 ± 0.627 vs.0.512 ± 0.228,t =9.722,P ＜ 0.05).The expression of TLR-3 mRNA/β-actin in PBMC of children with INS before treatment (the active group) (0.987 ± 0.124) was significantly higher than that in the remission group (0.501 ± 0.016) and the healthy control group (0.021 ± 0.001),the differences were statistically significant (t =26.076,42.571,all P ＜ 0.05),and the remission group was significantly higher than that in healthy control group (t =163.732,P ＜ 0.05).The expression of TLR-9 mRNA/β-actin in PBMC of children with INS before treatment (activity group) (1.965 ±0.952) was significantly higher than that in the remission group (1.336 ±0.282) and the healthy control group (0.790 ±0.731),the differences were statistically significant (t =4.249,5.734,all P ＜ 0.05),and the remission group was significantly higher than that in healthy control group (t =4.541,P ＜ 0.05).The serum levels of albumin in children with INS before treatment (activity group) (23.62 ± 11.67) g/L was significantly lower than that in remission group (42.19 ± 16.33) g/L and healthy control group (46.88 ± 14.80) g/L,and the differences were statistically significant (t =-6.20,-7.58,all P ＜0.01).The serum levels of cholesterol in children with INS before treatment (the active group) (9.54 ±2.53) mmol/L was significantly higher than that in the remission group (3.01 ± 1.72) mmoL/L and the healthy control group (2.89 ± 1.66) mmol/L,and the differences were statistically significant (t =14.32,12.677,all P ＜ 0.01).The serum levels of albumin and cholesterol in children with INS after treatment were not statistically significant difference compared to the healthy control group (t =-1.264,0.30,all P ＞ 0.05).The correlation analysis showed that there was a negative correlation between the expressions of TLR-1,TLR-3 and TLR-9 mRNA and the serum level of albumin in PBMC of children with INS before treatment (r =-0.457,-0.891,-0.125,respectively,all P ＜ 0.05).However,there was a positive correlation between the expressions of TLR-1,TLR-3 and TLR-9 mRNA and the serum level of cholesterol (r =0.445,0.911,0.872,all P ＜ 0.05).Conclusions The expressions of TLR-1,TLR-3 and TLR-9 mRNA in PBMC of children with INS were significantly higher and correlated with activity of disease.

Objective: To investigate expressions of Toll-like receptor(TLR)-2, TLR-4 and TLR-6 in peripheral blood mononuclear cells (PBMC) and serum immunoglobulin G (IgG) and IgM levels in pediatric idiopathic nephrotic syndrome (INS). The correlation between Toll-like receptors (TLR-2, TLR-4 and TLR-6) and serum immunoglobulin levels (IgG and IgM) will be proven in the pathogenesis of childhood INS in active stage (AS) and remission stage (RS). Methods: Forty-two INS patients (experimental group, 32 boys, 10 girls) and 29 healthy individuals (healthy control group, 19 boys, 10 girls) were enrolled in the present study from June, 2017 to October, 2018 in the First Affiliated Hospital of Xinxiang Medical University. There were no significant differences in gender (χ²=0.966, P=0.326) and age (t=-0.139, P=0.89) between 2 groups.TLR-2 mRNA, TLR-4 mRNA and TLR-6 mRNA expressions of PBMC were evaluated by using real-time PCR in both INS children with AS and RS and healthy children.The blood samples were drawn to detect by way of immunoturbidimetry serum immunoglobulin (IgG and IgM) levels in both INS children with AS and healthy children.The correlation between Toll-like receptors (TLR-2 mRNA, TLR-4 mRNA, TLR-6 mRNA) and serum immunoglobulin (IgG, IgM) levels were analyzed by using spearman correlation analysis. Results: The expression levels of TLR-2 mRNA in INS children with AS, RS and healthy children were 1.85±0.30, 1.00±0.23 and 0.85±0.12, respectively, and the expression levels of TLR-4 mRNA were 1.24±0.27, 0.80±0.23 and 0.68±0.09, respectively, while the expression levels of TLR-6 mRNA were 1.35±0.23, 0.92±0.19 and 0.79±0.15, respectively, so the differences were statistically significant(F=198.453, 67.013, 82.405, all P<0.01). The serum IgG level(2.90±0.89) g/L was lower in INS children with AS compared with the controls(9.21±1.88) g/L.However, the serum IgM level (2.87±0.96) g/L was higher in INS children with AS when compared with the controls(1.48±0.30), and the differences were statistically significant(t=-16.810, 8.701, all P<0.05). No significant correlation was noted between Toll-like receptors(TLR-2 mRNA, TLR-4 mRNA, TLR-6 mRNA) and serum immunoglobulin levels (IgG, IgM) (all P>0.05). Conclusions The results indicate that Toll-like receptors (TLR-2, TLR-4 and TLR-6) and immunoglobulin (IgG, IgM) might play a role in the pathogenesis of pediatric INS via distinct pathway.

Objective: To observe the relationship between impaired myocardial untwisting and left ventricular diastolic dysfunction in patients with autoimmune diseases (AD). Methods: In this retrospective study, 95 AD patients (27 males, (38.6±14.2) years old) were enrolled as AD group and 71 gender and age matched healthy subjects (24 males, (37.6±12.2) years old) were enrolled as control group, all underwent transthoracic echocardiography and two-dimensional speckle-tracking echocardiography (STE) in our hospital between January 2014 and June 2018. Left ventricular untwisting and diastolic function parameters were measured. Multiple logistic regression analysis was used to identify related factors of left ventricular diastolic dysfunction in AD patients. Receiver operating characteristic (ROC) curve was used to identify the diagnosis value of untwisting parameters for left ventricular diastolic dysfunction in AD patients. Results: Compared with control group, left ventricular ejection fraction was lower (58(47, 66)% vs. 67 (62, 71) %, P<0.001), E/e′ was higher (10.78 (7.28, 13.65) vs. 6.30 (5.55, 7.25) , P<0.001), isovolumic relaxation time was longer (73.5 (56.5, 88.0) ms vs. 62.0 (58.0, 68.5) ms, P<0.001),and untwist slope during isovolumic relaxation period (USIR) was lower (31.92 (14.09, 54.92) °/s vs. 59.90 (40.09, 87.18) °/s, P<0.001) in AD group than in control group. Multiple logistic regression analysis showed heart rate (OR=0.885, 95%CI 0.840-0.931, P<0.001), E/e′ (OR=0.655, 95%CI 0.537-0.798, P<0.001) and USIR (OR=0.986, 95%CI 0.974-0.998, P=0.020) were independently related with left ventricular diastolic dysfunction in AD patients. ROC curve showed that area under the curve (AUC) was 0.919 (P<0.001), sensitivity was 87.6%, and specificity was 88.7%, when combining the heart rate, E/e′, and USIR as assessment parameters for the diagnosis of left ventricular diastolic dysfunction in AD patients at a cutoff of 0.51. Conclusions Impairment of myocardial untwisting indicates the presence of early stage left ventricular diastolic dysfunction in AD patients. USIR may be a sensitive parameter to evaluate early stage left ventricular diastolic dysfunction in AD patients.

Objective:To explore the clinical characteristics and variant of CREBBP gene in a fetus with Rubinstein-Taybi syndrome (RSTS). Methods:A fetus with RSTS diagnosed at the Third Affiliated Hospital of Zhengzhou University in August 2022 was selected as the study subject. Clinical data, amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:Foot malformation, cerebellar vermis agenesis, brain agenesis, polysyndactyly of the big toes and other phenotypes were found by prenatal ultrasound. WES revealed that the fetus has harbored a heterozygous c. 4684G>T (p.E1562*) variant in exon 28 of the CREBBP gene (NM_004380.3), which was de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PVS1+ PS2_Moderate+ PM2_Supporting). After genetic counseling, the couple had opted to terminate the pregnancy and refused autopsy for the fetus. Conclusion:The c. 4684G>T (p.E1562*) variant of the CREBBP gene probably underlay the RSTS in this fetus. The newly discovered variant has enriched the mutational spectrum of the CREBBP gene and illustrated that WES is an efficient tool for the prenatal diagnosis of RSTS.

This article reported a case of neurodevelopmental disorder accompanied by spastic diplegia and visual impairment with the manifestation of small fetal head circumference. Prenatal ultrasonography performed at 33 +5 weeks of pregnancy revealed small fetal head circumference (-2.61SD) and oligohydramnios. Whole-exome sequencing identified a heterozygous frameshift variation of c.1623_1624insA (p.R542Tfs*30) in the CTNNB1 gene (NM_001904.4) of the fetus. No phenotypic abnormalities or corresponding gene variations were detected in the parents, suggesting it was a de novo variation. Based on the clinical manifestations, the fetus was diagnosed with a neurodevelopmental disorder accompanied by spastic diplegia and visual defects. Following genetic counseling, the pregnant woman chose to terminate the pregnancy.