Effect of exercise rehabilitation and adapted physical activity on psychomotor skills, motor abilities and motor development in children and adolescents with spastic cerebral palsy: an evidence-based research using ICF / 中国康复理论与实践

ObjectiveTo systematically review the evidences of impact of exercise rehabilitation and adapted physical activity on psychomotor skills, motor abilities, and motor development in children with spastic cerebral palsy (CP). MethodsRelevant literature was retrieved from PubMed, Embase, Web of Science and CNKI, from January, 2010 to June, 2023. The contents were coded using International Classification of Diseases, Eleventh Revision, and International Classification of Functioning, Disability and Health; and evidences were analyzed with theoretical framework and code of ICD-11 and ICF. ResultsA total of nine articles were included, from Denmark, South Korea, Australia, Saudi Arabia, Ghana, India and Japan, published from 2015 to 2022. The intervention programs primarily involved exercise rehabilitation (including physical therapy) and adapted physical activity. Exercise rehabilitation included upper limb strength training, lower limb strength training, balance and coordination training, gait training, functional aerobic exercise, stretching and flexibility exercises, flexibility training, muscle relaxation techniques; ten to 50 minutes a time, two to six times a week,with the intensity of low to high, for six to 20 weeks. Adapted physical activities mainly involved adapted running training, virtual games; 60 minutes a time, two to four times a week, with the intensity of medium to high, for six to twelve weeks. Interventions primarily took place in medical and rehabilitation institutions, schools, and home-based communities, with professionals including occupational physical therapists, university researchers, community health personnel and teachers. The outcomes were mainly reflected in four aspects: psychomotor skills, motor abilities, motor development, and quality of life and well-being. In terms of psychomotor skills, adolescents with CP mastered running techniques and knowledge, and enhanced their response to balance threats. In terms of motor abilities, adolescents with CP showed an increase in muscle strength, enhanced muscle endurance, and an expansion of muscle tone; improvements in gait functionality, walking ability, and gait symmetry; increases in walking endurance; improvements in standing function; and improvements in dynamic balance; as well as enhanced control over balance posture. In terms of motor development, there was a significant improvement in activities of daily living, participation levels in school and leisure activities during free time, and an expanded range of motion. In terms of quality of life and well-being, adolescents with CP showed significant enhancements in self-confidence and self-esteem, significant relief from (spastic) pain, and improvements in social well-being and acceptance. ConclusionThis systematic review has synthesized the evidences of benefits of exercise rehabilitation and adapted physical activity on the psychomotor skills, motor abilities and motor development of children and adolescents with spastic CP. In terms of psychomotor skills, exercise rehabilitation and adapted physical activity help to improve the cognitive and motor skills of adolescents with spastic CP. In terms of motor abilities, exercise rehabilitation and adapted physical activity can improve muscle-related functions, gait and walking abilities, as well as balance and coordination. In terms of motor development, exercise rehabilitation and adapted physical activity significantly enhance activities of daily living and the level of participation in leisure physical activities. Finally, exercise rehabilitation and adapted physical activity can increase energy and motivation, alleviate pain, and enhance social well-being and acceptance.

Cancer-associated fibroblast-derived PAI-1 promotes lymphatic metastasis via the induction of EndoMT in lymphatic endothelial cells.

BACKGROUND: Endothelial-mesenchymal transition (EndoMT) is an emerging adaptive process that modulates lymphatic endothelial function to drive aberrant lymphatic vascularization in the tumour microenvironment (TME); however, the molecular determinants that govern the functional role of EndoMT remain unclear. Here, we show that cancer-associated fibroblast (CAF)-derived PAI-1 promoted the EndoMT of lymphatic endothelial cells (LECs) in cervical squamous cell carcinoma (CSCC). METHODS: Immunofluorescent staining of α-SMA, LYVE-1 and DAPI were examined in primary tumour samples obtained from 57 CSCC patients. Assessment of cytokines secreted by CAFs and normal fibroblasts (NFs) was performed using human cytokine antibody arrays. The phenotype of EndoMT in lymphatic endothelial cells (LECs), gene expression levels, protein secretion and activity of signaling pathways were measured by real-time RT-PCR, ELISA or western blotting. The function of lymphatic endothelial monolayers was examined by transwell, tube formation assay, transendothelial migration assay in vitro. Lymphatic metastasis was measured using popliteal lymph node metastasis model. Furthermore, association between PAI-1 expression and EndoMT in CSCC was analyzed by immunohistochemistry. The Cancer Genome Atlas (TCGA) databases was used to assess the association of PAI-1 with survival rate in CSCC. RESULTS: CAF-derived PAI-1 promoted the EndoMT of LECs in CSCC. LECs undergoing EndoMT could initiate tumour neolymphangiogenesis that facilitated cancer cell intravasation/extravasation, which in turn promoted lymphatic metastasis in CSCC. Mechanistically, PAI-1 activated the AKT/ERK1/2 pathways by directly interacting with low-density lipoprotein receptor-related protein (LRP1), thereby leading to elevated EndoMT activity in LECs. Blockade of PAI-1 or inhibition of LRP1/AKT/ERK1/2 abrogated EndoMT and consequently attenuated CAF-induced tumour neolymphangiogenesis. Furthermore, clinical data revealed that increased PAI-1 levels positively correlated with EndoMT activity and poor prognosis in CSCC patients. CONCLUSION: Our data indicate that CAF-derived PAI-1 acts as an important neolymphangiogenesis-initiating molecular during CSCC progression through modulating the EndoMT of LECs, resulting in promotion of metastasis ability in primary site. PAI-1 could serve as an effective prognostic biomarker and therapeutic target for CSCC metastasis.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease / 北京大学学报(医学版)

OBJECTIVE@#To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD).@*METHODS@#This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD.@*RESULTS@#There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE.@*CONCLUSION@#Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.

Anti-endothelial cell antibodies in predicting early miscarriage / 北京大学学报(医学版)

OBJECTIVE@#To explore the clinical significance of anti-endothelial cell antibodies (AECA) in predicting early miscarriage.@*METHODS@#A total of 122 pregnant women with no history of autoimmune diseases who underwent prenatal examination at Peking University People's Hospital from January 2020 to December 2022 were selected, and they were tested for AECA. Based on the history of early miscarriage (gestational age at miscarriage < 12 weeks), the participants were divided into an early miscarriage group and a control group. t-tests, non-parametric Wilcoxon tests, Chi-square tests, and Fisher's exact probability method were used to compare general information and laboratory indicators between the two groups. A multivariate Logistic regression model was used to analyze the factors associated with early miscarriage. The natural miscarriage rates were assessed through follow-up with pregnant women, and Kaplan-Meier survival analysis was employed to compare the natural miscarriage rates between AECA-positive and AECA-negative pregnant women.@*RESULTS@#(1) A total of 122 pregnant women were enrolled, comprising 35 cases (28.7%) in the early miscarriage group, with an average age of (32.1±6.1) years, and 87 cases (71.3%) in the control group, with an average age of (30.7±5.1) years. The early miscarriage group had higher gravidity [3 (2, 4) vs. 1 (1, 2), Z=-6.402, P < 0.001] and a higher prevalence of hypertension (11.4% vs.1.1%, P=0.024). The positive rate of AECA in the early miscarriage group (34.3% vs. 8.0%, χ2=13.070, P < 0.001) and the proportion of elevated immunoglobulin G (17.1% vs. 4.6%, P=0.032) were significantly higher than that in the control group. (2) Multivariate logistic regression analysis showed that higher gravidity (OR=4.149, 95%CI: 2.287-7.529, P < 0.001), AECA positivity (OR= 4.288, 95% CI: 1.157-15.893, P=0.029), and elevated immunoglobulin G levels (OR =6.177, 95%CI: 1.156-33.015, P=0.033) were risk factors for early miscarriage. (3) The 122 pregnant women were categorized into two groups: the AECA-positive group (19 cases) and the AECA-negative group (103 cases). Survival analysis demonstrated that at the end of 12 weeks of gestation, the fetal survival rate in the AECA-positive group was significantly lower than that in the AECA-negative group (84.2% vs. 96.1%, P= 0.035).@*CONCLUSION@#Higher gravidity, AECA positivity, and elevated immunoglobulin G levels are significant risk factors for early miscarriage. The results demonstrate that AECA is a novel predicting test in early miscarriage.

MiR-525-5p Regulates Migration, Invasion and Proliferation of Glioma Cells Through Targeted Binding of PLIN3 / 中国生物化学与分子生物学报

The most common type of intracranial malignancy is glioma. Although the current treatments are surgery, radiation and chemotherapy, the prognosis for patients with glioma is not promising. Therefore, it becomes critical to find an effective management. The literature shows that microRNA (miRNA) plays an important role in tumorigenesis and progression. Based on this, this study aimed to investigate the molecular mechanism of miR-525-5p in regulating the migration, invasion and proliferation of glioma cells. The TCGA database was used to identify perilipin 3 (PLIN3) differentially expressed in normal tissues and glioma tissues, and the CGGA and GEPIA databases were used to query that high expression of PLIN3 was associated with poor prognosis in glioma patients and Western blot experiments revealed that PLIN3 was highly expressed in glioma cells (P<0. 05) . The results of wound healing assay and Transwell invasion assay showed that knockdown or overexpression of PLIN3 respectively inhibited or promoted the migration and invasion of glioma cells (P < 0. 05) . Dual luciferase assays confirmed that PLIN3 could bind to miR-525-5p target. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) showed that miR-525-5p expression was lower in LN229 and U251 glioma cells than in human astrocyte (HA) (P < 0. 05) . Transwell assay and 5-ethynyl-2-deoxyuridine (EdU) cell proliferation assay verified that down- or up-regulation of miR-525-5p could reverse the effects of overexpression or knockdown of PLIN3 on LN229 glioma cells (P<0. 05) . Taken together, miR-525-5p was able to regulate the migration, invasion and proliferation of glioma cells by targeting PLIN3.

Evaluation of Visual Acuity of Ametropia with Visual Event-Related Potential Nogo-P3 Component / 法医学杂志

OBJECTIVES@#To analyze the Nogo-P3 component of event-related potential (ERP) in the process of visual acuity processing, to provide electrophysiological evidence for objective evaluation of visual acuity.@*METHODS@#Twenty-six subjects with no other ocular diseases except for ametropia were recruited, and all subjects had uncorrected visual acuity both eyes 1/10 (evaluated using Monoyer chart). Block letter E with different visual angles and directions were used as graphic stimuli. The Go/Nogo paradigm was used for ERP studies. The visual angle of Go stimulation angle was 1°15', Nogo stimuli were 1°15', 55', 24' and 15'. The visual acuity test was performed on each of the two naked eyes separately in all subjects, and the characteristics of the Nogo-P3 component were analyzed.@*RESULTS@#The latency of Nogo-P3 showed no difference between the stimuli of 1°15' and 55', and between Nogo stimulation angle 24' and 15'. There was significant difference between Nogo stimulation angle 1°15' and 24', and between Nogo stimulation angle 1°15' and 15' (P<0.05). There was significant difference between Nogo stimulation angle 55' and 24', and between Nogo stimulation angle 55' and 15' (P<0.05). No significant differences were observed in the Nogo-P3 amplitude among Nogo stimulation.@*CONCLUSIONS@#In the Go/Nogo paradigm, Nogo-P3 can reflect the cognitive response of subjects to Nogo stimulation, which can be used for objective evaluation of visual acuity.

Tumor-secreted exosomal Wnt2B activates fibroblasts to promote cervical cancer progression.

The activation of stromal fibroblasts into cancer-associated fibroblasts (CAFs) has been suggested to promote primary tumor growth and progression; however, the mechanisms underlying the crosstalk between tumors and fibroblasts that drives stromal heterogeneity remain unknown. Here, we show that high Wnt2B levels were positively correlated with the number of CAFs in cervical cancer (CC). More importantly, Wnt2B was characteristically enriched in CC cell-secreted exosomes and transferred into fibroblasts to promote fibroblast activation via Wnt/ß-catenin signaling, and inhibiting exosomal release or the Wnt/ß-catenin signaling pathway diminished the activation induced by exosomal Wnt2B. Moreover, circulating exosomal Wnt2B also promoted CAF conversion in vitro and its expression was significantly higher in CC patients. In conclusion, our findings indicate that CC cell-derived Wnt2B can induce the activation of fibroblasts into CAFs, mainly via exosome-dependent secretion, thus providing directions for the development of diagnostic and therapeutic targets for CC progression.

A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner.

Lymphatic remodelling in the hypoxic tumour microenvironment (TME) is critically involved in the metastasis of cervical squamous cell carcinoma (CSCC); however, its underlying mechanisms remain unclear. Here, we uncovered a novel lymphatic pattern in the hypoxic TME, wherein lymphatic vessels (LVs) are encapsulated by tumour-associated macrophages (TAMs) to form an interconnected network. We describe these aggregates as LVEM (LVs encapsulated by TAMs) considering their advantageous metastatic capacity and active involvement in early lymph node metastasis (LNM). Mechanistic investigations revealed that interleukin-10 (IL-10) derived from hypoxic TAMs adjacent to LVs was a prerequisite for lymphangiogenesis and LVEM formation through its induction of Sp1 upregulation in lymphatic endothelial cells (LECs). Interestingly, Sp1high LECs promoted the transactivation of C-C motif chemokine ligand 1 (CCL1) to facilitate TAM and tumour cell recruitment, thereby forming a positive feedback loop to strengthen the LVEM formation. Knockdown of Sp1 or blockage of CCL1 abrogated LVEM and consequently attenuated LNM. Notably, CSCCnon-LNM is largely devoid of hypoxic TAMs and the resultant LVEM, which might explain its metastatic delay. These findings identify a novel and efficient metastasis-promoting lymphatic pattern in the hypoxic TME, which might provide new targets for anti-metastasis therapy and prognostic assessment.

Periostin+ cancer-associated fibroblasts promote lymph node metastasis by impairing the lymphatic endothelial barriers in cervical squamous cell carcinoma.

Lymph node metastasis (LNM), a critical prognostic determinant in cancer patients, is critically influenced by the presence of numerous heterogeneous cancer-associated fibroblasts (CAFs) in the tumor microenvironment. However, the phenotypes and characteristics of the various pro-metastatic CAF subsets in cervical squamous cell carcinoma (CSCC) remain unknown. Here, we describe a CAF subpopulation with elevated periostin expression (periostin+ CAFs), located in the primary tumor sites and metastatic lymph nodes, that positively correlated with LNM and poor survival in CSCC patients. Mechanistically, periostin+ CAFs impaired lymphatic endothelial barriers by activating the integrin-FAK/Src-VE-cadherin signaling pathway in lymphatic endothelial cells and consequently enhanced metastatic dissemination. In contrast, inhibition of the FAK/Src signaling pathway alleviated periostin-induced lymphatic endothelial barrier dysfunction and its related effects. Notably, periostin- CAFs were incapable of impairing endothelial barrier integrity, which may explain the occurrence of CAF-enriched cases without LNM. In conclusion, we identified a specific periostin+ CAF subset that promotes LNM in CSCC, mainly by impairing the lymphatic endothelial barriers, thus providing the basis for potential stromal fibroblast-targeted interventions that block CAF-dependent metastasis.

Significance and research status of quality management of cardiopulmonary resuscitation training for Chinese public / 中国实用护理杂志

The quality of public cardiopulmonary resuscitation training plays an important role in improving the survival rate of patients with cardiac arrest. Various forms of training have been carried out all over China, which plays a great role in promoting the work of cardiopulmonary resuscitation. However, there is still a lot of room for improvement in the quality management and effect sustainability of training. This paper reviews the current situation and deficiencies of quality management of public cardiopulmonary resuscitation training, and the role of training quality in enhancing people's self-confidence in learning and rescue, training contents, training methods, quality evaluation indicators, evaluation methods, and quality influencing factors and retraining time requirements, and so on. And it puts forward some practical suggestions on the quality management of public cardiopulmonary resuscitation training in China. Such as it will more emphasize standardized training, deliberate practice, proficient training, National Training, long-term maintenance of knowledge and skills, and using useful tools to improve the quality of cardiopulmonary resuscitation training, etc. In order to improve the training quality management level of the public, so that the trainees can really master cardiopulmonary resuscitation skills, so as to improve the rescue rate and survival rate of patients with cardiac arrest. To promote the sustainable development of people's health.

Clinical characteristics and risk factors of rheumatoid arthritis with ulcerative keratitis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical characteristics, risk factors and prognosis of ulcerative keratitis (UK) in patients with rheumatoid arthritis (RA).@*METHODS@#Sixteen patients with UK (the UK group) were screened among 4 773 RA patients hospitalized at Peking University People's Hospital from January 2003 to May 2021, and 72 patients with RA without UK in the control group were selected by propensity score matching (PSM). The clinical features, laboratory data and medications between the two groups were collected and analyzed.@*RESULTS@#The average age of the patients with RA was 60 years at the time of the complication of UK. UK appeared on average in the 16th year of RA, with the majority of UK occurring in the 7th year of RA and beyond (14 cases), however, a minority of UK was the first symptom of RA (1 case). UK associated with RA manifested as simple marginal UK in 8 cases, marginal UK with perforation in 5 cases, marginal UK with uveitis in 2 cases and central UK with perforation in 1 case. The number of swollen joints was significantly higher in the UK group than in the control group [6.0(2.5, 23.0) vs. 3.0(1.0, 9.8), Z=-2.047, P=0.041], and the proportion of secondary Sjögren syndrome (SS, 37.5% vs. 6.9%, χ2=11.175, P=0.004) and interstitial lung disease (ILD, 37.5% vs. 8.3%, χ2=9.456, P=0.008) were significantly higher in the RA patients with UK than the patients without UK. The uses of sulfasalazine (12.5% vs. 48.6%, χ2=7.006, P=0.008), leflunomide (31.3% vs. 63.9%, χ2=5.723, P=0.017) and gold salt(6.3% vs. 33.8%, χ2=4.841, P=0.032)were significantly lower in the UK group than in the control group. However, there was no statistically significant comparison between the two groups for the 28-joint disease activity score-erythrocyte sedimentation rate (5.3±1.8 vs. 5.1±1.6, t=0.309, P=0.761). Logistic analysis showed the number of swollen joints (OR=1.148), secondary SS (OR=79.118), complicated with ILD (OR=6.596) and the use of sulfasalazine (OR=0.037) were independent relevant factors (P < 0.05) for UK in RA patients.@*CONCLUSION@#The number of swollen joints, secondary SS, complicated with ILD and the use of sulfasalazine are independent relevant factors for UK in patients with RA.

Comparison of ASSR, ABR and 40 Hz AERP Response Thresholds at Different Frequencies and Their Forensic Applications / 法医学杂志

OBJECTIVES@#To explore the relationship between the frequency characteristics and response threshold of auditory steady-state response (ASSR), auditory brainstem response (ABR) and 40 Hz auditory event related potential (40 Hz AERP), and their application values in forensic medicine.@*METHODS@#Thirty volunteers with normal hearing (60 ears) were selected to perform pure tone audiometry (PTA) threshold and ASSR, ABR and 40 Hz AERP response threshold tests in the standard sound insulation shielding room, and the results were statistically analyzed by SPSS 22.0 software.@*RESULTS@#At 0.5 kHz and 1.0 kHz frequencies, the correlation between 40 Hz AERP response threshold and PTA threshold was good, which was better than that of ASSR and ABR response threshold. At 2.0 kHz and 4.0 kHz frequencies, the correlation between ASSR and ABR response thresholds and PTA threshold was good, which was better than that of 40 Hz AERP response threshold.@*CONCLUSIONS@#To evaluate the hearing at 0.5 kHz and 1.0 kHz frequencies, it is recommended to use 40 Hz AERP and ASSR to comprehensively assess the PTA threshold of the subjects. To evaluate the hearing at 2.0 kHz and 4.0 kHz frequencies, ABR and ASSR are recommended to assess the PTA threshold of subjects comprehensively. The combination of ASSR, ABR and 40 Hz AERP can improve the accuracy of hearing function evaluation.

Impacts of smoking status on the clinical outcomes of coronary non-target lesions in patients with coronary heart disease: a single-center angiographic study / 中华医学杂志(英文版)

BACKGROUND@#Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions.@*METHODS@#Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes.@*RESULTS@#A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1] % vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P = 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P = 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P = 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P = 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P = 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04-8.62, P = 0.042).@*CONCLUSION@#Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.

Frequency Characteristics of AEPs in Normal Young Adults and Comparison of Their Response Threshold and Pure Tone Audiometry Threshold / 法医学杂志

Objective The tests of three types of auditory evoked potentials （AEPs） were performed on normal young adults, to understand the frequency characteristics of different testing methods and the relationship between response threshold and pure tone audiometry threshold of different methods, and to discuss the forensic value of 3 types of AEPs to evaluate hearing function. Methods Twenty normal young adults were selected, their standard pure tone audiometry threshold, short-term pure tone audiometry threshold and the response threshold of 3 types of AEPs （tone burst-auditory brainstem response, 40 Hz auditory event-related potential and slow vertex response） at 0.5 kHz, 1.0 kHz, 2.0 kHz and 4.0 kHz were recorded. The relationship between the response threshold and standard pure tone audiometry threshold, short-term pure tone audiometry threshold of 3 types of AEPs at different frequencies as well as the differences between different types of AEPs were analyzed. Results The short-term pure tone audiometry threshold was higher than the standard pure tone audiometry threshold at each frequency. The response threshold and standard pure tone audiometry threshold of the 3 types of AEPs all had a certain correlation, and the response threshold of the 3 types of AEPs was higher than short-term pure tone audiometry threshold and standard pure tone audiometry threshold at each frequency. The differences in the differences between the response threshold and standard pure tone audiometry threshold of the 3 types of AEPs at different frequencies had statistical significance. Linear regression mathematical models were established to infer the standard pure tone audiometry threshold （hearing level） from response threshold （sound pressure level） of 3 types of AEPs of normal young adults. Conclusion When using response threshold of different types of AEPs to estimate pure tone audiometry threshold, conversion and correction are needed. Combined use of different types of AEPs could improve the accuracy of hearing function evaluation.

Hypoxia-induced ZEB1 promotes cervical cancer progression via CCL8-dependent tumour-associated macrophage recruitment.

The accumulation of tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is associated with malignant progression in cancer. However, the mechanisms by which the hypoxic TME facilitates TAM infiltration are not fully understood. This study showed that high ZEB1 expression in hypoxic cervical cancer cell islets was positively correlated with CD163+ TAM accumulation. ZEB1 in hypoxic cancer cells promoted the migration of TAMs in vitro and altered the expression of multiple chemokines, especially CCL8. Mechanistically, hypoxia-induced ZEB1 activated the transcription of CCL8, which attracted macrophages via the CCR2-NF-κB pathway. Furthermore, ZEB1 and CCL8 were independent prognostic factors in cervical cancer patients based on The Cancer Genome Atlas (TCGA) data analysis. In conclusion, hypoxia-induced ZEB1 exerts unexpected functions in cancer progression by fostering a prometastatic environment through increased CCL8 secretion and TAM recruitment; thus, ZEB1 may serve as a candidate biomarker of tumour progression and provide a potential target for disrupting hypoxia-mediated TME remodelling.

Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma.

AIMS: Recently, cancer-derived exosomes were shown to have pro-metastasis function in cancer, but the mechanism remains unclear. Angiogenesis is essential for tumor progression and is a great promising therapeutic target for advanced cervical cancer. Here, we investigated the role of cervical cancer cell-secreted exosomal miR-221-3p in tumor angiogenesis. METHODS AND RESULTS: miR-221-3p was found to be closely correlated with microvascular density in cervical squamous cell carcinoma (CSCC) by evaluating the microvascular density with immunohistochemistry and miR-221-3p expression with in situ hybridization in clinical specimens. Using the groups of CSCC cell lines (SiHa and C33A) with miR-221-3p overexpression and silencing, the CSCC exosomes were characterized by electron microscopy, western blotting, and fluorescence microscopy. The enrichment of miR-221-3p in CSCC exosomes and its transfer into human umbilical vein endothelial cells (HUVECs) were confirmed by qRT-PCR. CSCC exosomal miR-221-3p promoted angiogenesis in vitro in Matrigel tube formation assay, spheroid sprouting assay, migration assay, and wound healing assay. Then, exosome intratumoral injection indicated that CSCC exosomal miR-221-3p promoted tumor growth in vivo. Thrombospondin-2 (THBS2) was bioinformatically predicted to be a direct target of miR-221-3p, and this was verified by using the in vitro and in vivo experiments described above. Additionally, overexpression of THBS2 in HUVECs rescued the angiogenic function of miR-221-3p. CONCLUSIONS: Our results suggest that CSCC exosomes transport miR-221-3p from cancer cells to vessel endothelial cells and promote angiogenesis by downregulating THBS2. Therefore, CSCC-derived exosomal miR-221-3p could be a possible novel diagnostic biomarker and therapeutic target for CSCC progression.