Treatment of patent ductus arteriosus in very preterm infants in China / 中华儿科杂志

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

Association between HLA-DRB1 gene polymorphisms and genetic susceptibility of early-onset severe preeclampsia / 中国当代儿科杂志

OBJECTIVES@#To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE).@*METHODS@#Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups.@*RESULTS@#Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05).@*CONCLUSIONS@#The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.

Effect of robot-assisted bilateral task-oriented upper limb training on upper limb function of patients with stroke / 中国康复理论与实践

ObjectiveTo investigate the effect of robot-assisted bilateral task-oriented upper limb training on upper limb function of patients with stroke. MethodsFrom January, 2021 to June, 2022, 52 patients with stroke in the Second Hospital of Jiaxing were enrolled and randomized into control group (n = 26) and experimental group (n = 26). Both groups received routine treatment. The control group added conventional bilateral upper limb training, while the experimental group added robot-assisted bilateral task-oriented upper limb training, for six weeks. Before and after treatment, the upper limb motor function and activities of daily living were assessed with Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and modified Barthel Index (MBI). The upper limb proprioception test system was used to measure the average trace error (ATE) and test execution time of the upper limb. ResultsBefore treatment, there was no significant difference in the scores of FMA-UE and MBI, and ATE and test execution time between two groups (P > 0.05). After treatment, all the indexes improved significantly in both groups (|t| > 5.400, P < 0.001), and were better in the experimental group than in the control group (|t| > 2.123, P < 0.05). ConclusionRobot-assisted bilateral task-oriented upper limb training could facilitate to improve the upper limb motor function and activities of daily living of stroke patients.

The effects of dynamic instability training on the postural control, balance and walking of stroke survivors / 中华物理医学与康复杂志

Objective:To observe any effect of dynamic motor instability training on the balance and postural control of stroke survivors.Methods:Forty stroke survivors with poor balance were randomly divided into a control group and an observation group, each of 20. In addition to routine rehabilitation, the observation group was given 20 minutes of dynamic motor instability training, 5 days a week for 8 weeks, while the control group underwent routine rehabilitation for the same length of time. Before and after the intervention, surface electromyogram of the rectus femoris, biceps femoris, and erector spinae were recorded during perturbation. Activation time and the intensity of the anticipatory and complementary postural adjustments (APAs and CPAs) were also observed. Balance and lower limb motor functioning were assessed using the Berg balance scale (BBS), the Fugl-Meyer lower extremity assessment (FMA-LE), and GaitWatch analysis.Results:After the treatment the average activation time of the rectus femoris, biceps femoris in the affected side and those of the biceps femoris [(-84.31±5.74)s] and erector spinae in the intact side in APAs were all significantly shorter in the observation group than in the control group, while the average activation intensity of the rectus femoris and erector spinae was significantly greater. There was no significant difference in the activation intensity of each muscle group in CPAs after the treatment. After the intervention the average BBS score, FMA-LE score, stride length and walking speed of the observation group all were significantly better than the control group′s averages.Conclusions:Supplementing traditional rehabilitation training with dynamic motor instability training can further improve the posture control of stroke survivors and promote recovery of their balance and walking ability.

An interview survey on the development of family doctor work mode in Shanghai Xuhui district / 中华全科医师杂志

Objective:To survey the status quo of family doctor work mode in Shanghai Xuhui district.Methods:Semi-structured and structured in-depth interviews were conducted in Shanghai Xuhui district from April to June 2021, 11 directors, 12 deputy directors in charge and 30 family doctors from 12 community health service centers participated in the survey and completed two stages and four sessions of interviews on the development of the integrated and high-quality family doctor work mode and the ways to realize and the challenges to face. The records of interviews were transcribed, sorted and analyzed using the Colaizzi 7-step analysis method.Results:The survey showed that the family doctor contracting was carried out in a large team mode in the whole district, mainly for the elderly, and most of contracted residents were not included in health management and follow-up services. The team was composed of family doctors and assistants, and the routine outpatient service was the main work pattern, and the regular services also included the chronic disease follow-up and health check-up for elderly. On the issue of how to output high-quality integrated services, the majority of doctors (12/13) believed that the contracted individual should be taken as the unit of fine service, carrying out overall health assessment, optimizing medication plan, lifestyle guidance, one-stop service in hospital, etc.; only one doctor suggested that the family should be the management unit. For upgrading the working mode and service quality, insufficient time and energy were the main obstacle. Public health work occupied a lot of working time, but it seemed not be transformed into favorable resources and conveniences in health management and services. The professional assistants should carry out some responsibility to save family doctor′s time. The survey suggests that informatization, service space, and sufficient drug supply are the keys for ensuring high-quality and high-efficiency integrated services.Conclusion:The organizational structure of the family doctor team in Shanghai Xuhui district is relatively mature, but the integrated and high-quality service output has not yet reached. It is necessary to make regional overall planning and increase efforts to achieve the integration of medical treatment and prevention, so as to gain time for family doctors to carry out high-quality services. At the same time, it is also necessary to cultivate effective family doctor assistants, provide an information work platform that matches the work attributes and goals of family doctors, open up an integrated health management service space, and ensure the full range supply of drugs.

Value of MRI Ovarian-Adnexal Reporting and Data System in Differentiating Benign and Malignant Ovarian-Adnexal Lesions / 中山大学学报(医学科学版)

ObjectiveTo explore the value of MRI ovarian-adnexal reporting and data system （O-RADS MRI） in differentiating benign and malignant ovarian-adnexal masses.MethodsTotally 146 patients （202 masses） with ovarian-adnexal lesions who underwent pelvic examination at 3.0 T MRI according to standardized scan protocol of O-RADS MRI and were pathologically confirmed in The First Affiliated Hospital of Sun Yat-sen University between January 2020 and February 2022 were retrospectively analyzed. Two radiologists classified the ovarian-adnexal masses as risk levels 1~5 according to O-RADS MRI and evaluated their consistency by Cohen’s kappa. Using pathological findings as the gold standard， the detection yield of malignant lesions with O-RADS MRI classification was analyzed. Sensitivity， specificity， accuracy， and the area under the receiver operating characteristic curve were calculated （cutoff for malignancy， score ≥ 4）.ResultsOf 202 masses， 62 （30.7%） were malignant， 140 （69.3%） were benign. The two radiologists presented good agreement in O-RADS MRI classification of ovarian adnexal masses （Kappa=0.932）. The malignancy rates of masses with scores of 1， 2， 3， 4 and 5 were 0%， 0%， 7.7%， 95%， 97.6%， respectively. Sensitivity， specificity， accuracy， and the area under the receiver operating characteristic curve were 96.8% （60/62）， 98.6% （138/140）， 98.0% （198/202）， 0.977.ConclusionsO-RADS MRI yields high diagnostic efficiency for benign and malignant ovarian adnexal masses and its widespread implementation will improve communication between radiologists and clinicians， and facilitate optimal patient management. Therefore， O-RADS MRI warrants widespread use in clinical setting.

T cell immunotherapy mediated by dual-affinity aptamer targeted liposome / 药学学报

Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.

Correlation analysis of vitamin D level and anti-Müllerian hormone in infertile female and the role in predicting pregnancy outcome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the relationship between serum 25(OH)D and anti-Müllerian hormone (AMH) among infertile females and their predictive impacts on in vitro fertilization and embryo transfer pregnancy outcome.@*METHODS@#Totally 756 infertile females treated with assisted reproductive technology were enrolled and divided into three groups according to their vitamin D levels (group A with serum 25(OH)D≤10 μg/L, group B with serum (10-20) μg/L, and group C with serum ≥20 μg/L). The serum AMH levels were detected. The differences among the groups were analyzed, as well as the correlation between vitamin D levels and serum AMH levels in various infertility types (fallopian tube/male factor, polycystic ovary syndrome (PCOS), ovulation disorders excluded PCOS, endometriosis, unexplained infertility, and others). Also, the predictive roles of vitamin D and AMH in pregnancy outcome in all the infertile females were discussed.@*RESULTS@#(1) 87.7% of the enrolled females were insufficient or deficient in vitamin D. (2) The serum AMH levels in the three groups with different vitamin D levels were 1.960 (1.155, 3.655) μg/L, 2.455 (1.370, 4.403) μg/L, 2.360 (1.430, 4.780) μg/L and there was no significant difference in serum AMH levels among the three groups (P>0.05). (3) Serum 25(OH)D and AMH levels presented seasonal variations (P < 0.05). (4) There was no prominent correlation between the serum AMH level and serum 25(OH)D level in females of various infertility types after adjusting potential confounding factors [age, body mass index (BMI), antral follicle count (AFC), vitamin D blood collection season, etc.] by multiple linear regression analysis (P>0.05). (5) After adjusting for confounding factors, such as age, BMI, number of transplanted embryos and AFC, the results of binary Logistics regression model showed that in all the infertile females, the serum AMH level was an independent predictor of biochemical pregnancy outcome (P < 0.05) while the serum 25(OH)D level might not act as a prediction factor alone (P>0.05). In the meanwhile, the serum 25(OH)D level and serum AMH level were synergistic predictors of biochemical or clinical pregnancy outcome (P < 0.05).@*CONCLUSION@#Based on the current diagnostic criteria, most infertile females had vitamin D insufficiency or deficiency, but there was not significant correlation between serum 25(OH)D and ovarian reserve. While vitamin D could not be used as an independent predictor of pregnancy outcome in infertile females, the serum AMH level could predict biochemical pregnancy outcome independently or jointly with vitamin D.

Robotic pelvic assistance better improves trunk control and walking after a stroke / 中华物理医学与康复杂志

Objective:To explore any effect of training assisted by a pelvic rehabilitation robot on trunk control and walking after cerebral infarction.Methods:Forty cerebral infarction survivors with hemiplegia were randomly divided into an experimental group and a control group, each of 20. Both groups were given routine neurological medication and rehabilitation training, while the experimental group was additionally provided with 20 minutes of robot-assisted gait training daily, five times a week, for 4 weeks. Before and after the intervention, the motor function, walking function, trunk control and pelvic movement were assessed using a simplified version of the Fugl-Meyer assessment (FMA-LL), functional ambulation categories (FAC) and the trunk control test (TCT).Results:After the treatment, significant improvement was observed in all of the above measurements in both groups. The average FMA-LL, FAC and TCT results of the experimental group as well as their average pelvic lateral displacement, height displacement, rotation angle and roll angle were all significantly superior to the control group′s averages.Conclusions:Robot-assisted training can effectively improve lower limb motor functioning, trunk control, walking and pelvic motion after cerebral infarction, with better curative effect than routine rehabilitation training alone.

Prognostic analysis of critically ill patients with coagulation dysfunction by thrombelastogram and coagulation 4 items combined APACHEⅡ score / 中国输血杂志

【Objective】 To explore the prognosis of critically ill patients with coagulation dysfunction using thrombelastogram(TEG) and coagulation four items combined with APACHEⅡ score. 【Methods】 From March 2017 to March 2020, 287 critically ill patients with coagulation dysfunction in our hospital were selected as the study group, and 303 patients with normal coagulation function during the same period were set as the control. The study group was divided into low-risk group(group A), intermediate-risk group(group B) and high-risk group (group C) based on the APACHEⅡ score, and into survival group and death group according to the prognosis. The difference of TEG, coagulation four items, and APACHEⅡ scores between the two groups were analyzed. The correlation and difference between TEG, coagulation four items and APACHE II score in the study group were analyzed. The ROC curve was drawn to analyze the prognostic predictive value of research indicators. 【Results】 Blood coagulation function related indicators in the study group fluctuated significantly: in comparison to the control, the CI value, MA value, and α angle were smaller, while the K time and R time were longer; among the coagulation four items, PT, APTT and TT were higher; Fg level was lower, and the APACHE Ⅱ score was higher(P0.05). There were significant differences between the TEG and coagulation function related index levels in patients with different prognosis. Compared with the survivals, the CI value, MA value and α angle of the dead group were smaller, while the K time and R time were longer; and among the coagulation four items, PT, APTT, and TT were higher, the Fg level was lower, and the APACHEⅡ score was higher (PP4\\P5>APACHE Ⅱ score>P1>P2. 【Conclusion】 TEG, coagulation four items, and APACHE Ⅱ score can be used to assess the severity of patients with severe coagulation dysfunction. and the combined application of the 3 indicators are of high value in predicting the prognosis of such patients, and can provide reference for clinical formulation or adjustment of intervention programs to correct coagulation dysfunction.

Robot assistance can improve lower limb function and knee proprioception after cerebral infarction / 中华物理医学与康复杂志

Objective:To explore the effect of a pelvis-assisting rehabilitation robot on lower limb function and knee proprioception after cerebral infarction.Methods:Forty hemiplegic cerebral infarction survivors were randomly divided into an experimental group and a control group, each of 20. Both groups were given routine neurological medication and rehabilitation training, while the experimental group was additionally provided with 20 minutes of robot-assisted gait training daily, five times a week for four weeks. Before and after the intervention, motor function, balance, walking function and knee joint proprioception were assessed using the simplified Fugl-Meyer lower limb assessment, the Berg balance scale, functional ambulation categorization and the Humac Norm isokinetic tester.Results:After the treatment, significant improvement was observed in all of the above measurements in both groups, but the improvements were significantly greater in the experimental group.Conclusions:Robotic pelvic assistance can effectively improve lower limb motor function, balance, knee proprioception and walking after cerebral infarction.

Effects of Osthole on Apoptosis and Autophagy of Human Tongue Cancer Tca8113 Cells / 中国医学科学院学报

Objective To investigate the effects of osthole on the proliferation,apoptosis,and autophagy of human tongue cancer Tca8113 cells and explore its possible mechanism of action. Methods Tca8113 cells were cultured

Association of mild cognitive impairment with incidence of falls in communities aged 55 and over / 中华疾病控制杂志

Objective To explore the association between mild cognitive impairment (MCI) and the risk of falls in community populations, so as to provide a reference for preventing falls in the elderly. Methods 826 community residents aged 55 years and older were enrolled in Wuzhong, Ningxia; cognitive function was assessed during the participants attending the basic public health examination, and self-report falling events were observed through telephone call survey after half a year. The incidence of falls among different populations was compared using unconditional Logistic regression model. Results A total of 521 participants completed the follow-up study, and 127 of them met criteria of MCI at baseline. 32 participants reported falling occurred during follow-up with a incidence of 6.1% (32/521), and the incidence of falls was higher (8.85%,23/260) in females than that of males (3.45%,9/261) (RR=2.56, P=0.010). The incidence among MCI group (9.45%,12/127) was 1.86 times of that among non-MCI group (RR=1.86, P=0.073). Under the controlling of demographic variables (gender, age and education level), there was no association between MCI and falls (RR=1.41, P=0.382). Conclusions The incidence of falls in the elderly communities is common, and females has higher risk of falls than males. There is no statistical association between MCI and risk of falls. Further validation is needed with large-sample studies in the future.

Morphological characteristics identification and molecular DNA barcoding analysis of Hippocampus spinosissimus / 中国中药杂志

The combination of morphological characteristics and DNA barcodes was used to a systematic study of Hippocampus spinosissimus,laying the foundation for rapid and accurate identification for the medical seahorse species. According to the reported literature and observation on seahorse samples,the typical characteristics of the H. spinosissimus include highly developed spiny,much short nose,single or double cheeks and strongly developed spines bordering pouch. Genomic DNAs of H. spinosissimus and other related seahorse species were extracted using the TIANamp Marine Animals DNA Kit. The COⅠ and ATP6 genes were amplified and sequenced in both directions. After the verification by Blast,the GC content,intraspecific and interspecific genetic distance,and the Neighbor joining( NJ) phylogenetic trees were analyzed by MEGA 7. The lengths of the COⅠ and ATP6 genes were 649 bp and 602-603 bp,respectively,with the average GC content of 39. 96% and 35. 37%. The maximum intraspecific genetic distances in H. spinosissimus based on COⅠ and ATP were both far less than the minimum interspecific genetic distance between H. spinosissimus and other seahorses,suggesting a significant barcoding gap. NJ analysis results of COⅠ and ATP6 exhibited that all H. spinosissimus species clustered together,indicating that the two DNA barcode could identify H. spinosissimus from other seahorses accurately and quickly. In addition,H. spinosissimus shared a close genetic relationship between H. kelloggi according to the NJ tree. Furthermore,there exits three stable subgroup structure of H. spinosissimus,indicating that COⅠ and ATP6 barcodes could be applied the indicator for the geographical ecology research of H. spinosissimus. The results obtained the typical morphological and molecular identification characteristics of H. spinosissimus,which played central roles for the development of species identification. This study provides an important basis data for expanding the medical seahorse resources and ensuring the safety of clinical medicine.

Pharmacognosy Identification of Hippocampus barbouri Based on the Combination of the Morphological Characteristics and DNA Barcodes / 中国药学杂志

OBJECTIVE: To obtain the key identification information of Hippocampus barbouri (H. barbouri), investigate the pharmacognosy of the seahorse adulteration H. barbouri, using the combination of morphological and DNA barcoding technique. METHODS: Typical morphological characteristics of H. barbouri were studied based on the observations according to the previous reports and traditional pharmacognosy methods. Genomic DNAs of H. barbouri and other related seahorse species were extracted and the DNA barcoding genes of COI, 16S and ATP6 sequences were amplified and sequenced, respectively. In order to determine advantages of three barcodes for the identification of hippocampus, MEGA 7 was performed to analyze the intraspecific and interspecific distances and construct the NJ phylogenetic trees based on three different barcoding genes. RESULTS: The most typical distinguishing features of H. barbouri included the streak of the nose, five radial lines in the eyelid, and the long and short intervals of the tail thorns. The lengths of COI, 16S and ATP6 sequences were 649-650, 574 and 603 bp, respectively, with the maximum K2P intraspecific distances were 0.012, 0.003 and 0.003, respectively. The intraspecific distances of the three barcodes were far smaller than the corresponding minimum K2P interspecific distances of H. barbouri and other seven related seahorse species, existing an obvious barcoding gap. The NJ phylogenetic trees based on COI, 16S and ATP6 sequences showed that H. barbouri samples formed of a group indicating that H. barbouri could be distinguished from other seahorse species through the three DNA barcoding markers. In addition, H. barbouri showed close genetic relationship with H. histrix according to the NJ trees. Furthermore, the NJ tree structures of COI and ATP6 were more stable than that of 16S. CONCLUSION: The pharmacognostical investigation bases on the morphological identification and DNA barcodes obtained the key identification information of H. barbouri, providing the possibility for quick and accurate identification of this species. The COI, 16S and ATP6 barcoding genes can be used for further molecular identification markers for seahorse species. This study provides a new technical method for the development and quality control of hippocampus.

Inhibition of regorafenib against UDP-glucuronosyltransferases / 药学学报

This study was designed to investigate the inhibitory effects of regorafenib (REG) on the catalytic activities of 12 kinds of human UGT isoforms and human liver microsomes (HLM) in vitro. The broader potential of REG to perpetrate drug-drug interactions (DDI) arising from UGT enzyme inhibition is predicted by in vitro-vivo extrapolation (IV-IVE). Fifty mixed HLM and 12 kinds of recombinant UGTs were utilized as enzyme sources to evaluation the inhibitory effects of REG against UGTs. 4-Methylumbelliferone (4-MU) as a nonselective substrate of UGTs except for UGT1A4, N-(3-carboxypropyl)-4-hydroxy-1,8-napht-halimide (NCHN) and N-butyl-4-(4-hydroxyphenyl)-1,8-naphthalimide (NPHN) as the specific fluorescent substrate of UGT1A1, and trifluoperazine (TFP) as the specific substrate of UGT1A4. The half maximal inhibitory concentration (IC50) was calculated via the nonlinear regression analysis using Graphpad Prism 6.0, the inhibition kinetic types were selected and evaluated based on the intersection location of Lineweaver-Burk plot and Dixon plot, and Ki values were determined by the second plot of slopes. The potential DDI risk based on UGT1A1 inhibition was also evaluated through the in vitro parameters. The results demonstrated that REG displayed strong inhibitory effects against UGT1A1, 1A7, 1A9, and 2B7. The IC50 values were from 0.15 to 6.6 μmol·L-1 and Ki values from 0.027 to 14 μmol·L-1. The REG exerted competitive inhibition against UGT1A1-mediated 4-MU-O-glucuronidation and UGT1A1-mediated NPHN-O-glucuronidation, while the inhibition of NCHN-4-O-glucuronide by REG was suited to noncompetitive inhibition in both HLM and recombinant UGT1A1. Likewise, REG exhibited a mixed efficacy in inhibition of UGT1A7-, UGT1A9-, and UGT2B7-catalyzed 4-MU-O-glucuronidation. The AUC ratio of UGT1A1 specific substrates NPHN and NCHN can be increased by 101% to 302% and 13% to 109%, respectively. These results suggest that much caution should be exercised when REG is co-administered with UGT1A1 substrates.

Trunk flexor and extensor strength and the kinematic parameters of gait among stroke survivors / 中华物理医学与康复杂志

Objective To correlate the isokinetic strength of stroke survivors' trunk flexors and extensors with the kinematic parameters of their gait.Methods Thirty stroke survivors and 30 healthy counterparts formed an observation group and a control group.The strength of everyone's trunk flexors and extensors was measured isokinetically,including the flexor peak torque (FPT),extensor peak torque (EPT) and the ratio of the two (F/E).The test velocities were 30°/s,60°/s and 90°/s.And the kinematic parameters of their gait,including the step length,stride,velocity,frequency,width and cycle time were measured using a 3D gait analysis system,as well as the percentage of stance phase,swing phase,double support phase and single support phase.Results No significant differences were found between the average FPT,EPT or F/E of the two groups at any of the three test velocities.At the 30°/s test velocity the average FPT,EPT and F/E of the observation group were all positively correlated with the average step length,stride,velocity,steps/min,width and cycle time,as well as with the stance phase,swing phase,double support phase and single support phase percentages.The strongest correlation was between F/E and velocity (r=0.57),followed by frequency (r=0.54).Conclusion litating the walking ability of stroke survivors and correcting their gait should focus on strengthening the trunk muscles and optimizing their coordination.

Study on the Anti-Endotoxin Activity of Human Endotoxin Binding Peptide P1 and P2 / 现代检验医学杂志

Objective To study the antiendotoxin activity of P1 and P2 based on the lipopolysacchride binding protein.Method P1 and P2 were designed and obtained.In vitro test,peripheral blood mononuclear cell(PBMC)were extracted from volun-teer 100ml venous blood,the experiment group was arranged as:control group,positive control group,LPS group,LPS+P1 (2 mg/L,5 mg/L,12.5 mg/L)group and LPS+P2(2 mg/L,5 mg/L,12.5 mg/L)group,TNF-α and IL-6 of supernatant liquor in every group were detectd by ELISA.In vivo,40 kunming rice were randomly divided into four groups with ten rice each group:control group,model group,LPS+P1 and LPS+P2 group,Pathologic changes of lung and liver tissues were ob-served by hematoxylin and eosin(HE)staining.Results The serum level of IL-6 and TNF-αin 12.5 mg/L P1 and 2 mg/L, 5 mg/L,12.5 mg/L P2 treatment group were lower than that in model group,the difference was statistically significant(all P<0.01).Serum level of TNF-αor IL-6 in 12.5 mg/L P2 treatment group were similar to that in PMB treatment group, and there was no statistically significant difference(P>0.05).Histologymorphology finding showed that central veins of liver and hepatic sinusoid congestion,hepatic cellular edema existed,occasionally,acidophilic change and spotty necrosis were found,pulmonary interstitial edema,focal hemorrhage,alveolar space stenosis existed.As regards 10 mg/kg P1 treatment group mice,hepatic cellular edema and pulmonary interstitial edema ameliorated.About 10 mg/kg P2 treatment group mice, veins of liver and hepatic sinusoid congestion obviously ameliorated,mild pulmonary interstitial edema exsited.Conclusion The results indicated P1 and P2 had antiendotoxin effect,in vivo and vitro,for 12.5 mg/L P2,its inhibition effect for TNF-αor IL-6 release was positive.

Robot-assisted upper limb therapy improves shoulder joint proprioception after stroke / 中华物理医学与康复杂志

Objective To explore the effect of robot-assisted therapy on the shoulder joint proprioception of convalescent stroke survivors.Methods Forty stroke survivors were enrolled and randomized into an experimental group (n =20) and a control group (n =20).Both groups received routine drug treatment and rehabilitation,including the traditional kinesitherapy,occupational therapy and physical therapy,but the experimental group was additionally provided with 20 minutes of robot-assisted upper limb therapy 6 times a week for 8 weeks.Before the intervention and at 4 and 8 weeks the multi-joint system (MJS) upper limb proprioception test system was used to evaluate the average trace error and test execution time of the upper limb.Shoulder joint proprioception was measured at 30° and 60° in intorsion and extorsion using an isokinetic dynamometer.Results Before the training there were no significant differences between the two groups in terms of any of the assessments.After 4 and 8 weeks of training,significant improvement was observed in the measurements,and those of the experimental group were significantly better than those of the control group at the same time points.Conclusion Robot-assisted therapy can facilitate the recovery of shoulder joint proprioception after a stroke.It is worthy of application in clinical practice.

Influence of calcineurin on apoptosis of pre-B lymphocytes and the leukemia cells derived from pre-B lymphocytes / 中国实验血液学杂志

This study was aimed to compare the differential expressions of calcineurin (PP2B, PP3) in the mouse Pre-B cell lines (S9) and the tumor cell lines (S4C2) derived from pre-B lymphocytes, and to clarify its possible mechanism involving in the leukemia cell apoptosis. The quantitative real-time PCR was used to detect the differential expressions of H2AX-associated phosphakinase ATM, ATR, DNA-PKs, JNK1, P38 and the γ-H2AX-related phosphatase PP1, PP2A, calcineurin, PP4, PP6, PP5 between S9 and S4C2 cell lines. CCK-8 assay and flow cytometry were used to detect the effect of imatinib (IM) and cyclosporine A (CsA) on cytotoxicity and apoptosis of 2 cell lines. The Western blot was used to detect the effects of 2 drugs on apoptosis of S9 and S4C2 cell lines. The results showed that the expression level of calcineurin gene in the leukemia cell S4C2 was about 3.5 times of that in S9 cells, while the expression of other genes in these 2 kinds of cells was not significantly different. The apoptosis and toxicity of IM and CsA on S4C2 cells was significantly stronger than that on S9 cells. The expression level of calcineurin in S4C2 cells was higher than that in S9 cells.When CsA inhibited the calcineurin activity, the expression of DNA damage marker γ-H2AX in S9 cells was significantly lower than that in S4C2 cells,while the expression level of γ-H2AX between the two cell lines was no significantly different after treatment with imatinib, the expression level of γ-H2AX in S9 cells was lower than that in S4C2 cells when the two drugs were combined. It is concluded that the calcineurin plays a role of anti-apoptosis in B leukemic cells, cyclosporine A can promote the leukemia cell apoptosis.