BACKGROUND:Intervertebral disc degeneration is an important cause of low back pain.At present,there are many modeling methods for disc degeneration in China and abroad,but there is not a model for low back pain due to disc degeneration. OBJECTIVE:To compare the effect of mechanical puncture combined with tumor necrosis factor α and complete Freund's adjuvant with a conventional disc mechanical puncture alone. METHODS:A total of 18 male adult Sprague-Dawley rats were randomly divided into 3 groups,with 6 animals in each group.No treatment was given in the blank group.Animal models of intervertebral disc degeneration were made in the L4-5 segments of rats in the control using conventional mechanical puncture.In the experimental group,on the basis of mechanical puncture,tumor necrosis factor α+complete Freund's adjuvant was injected into the L4-5 intervertebral discs using a microinjector to establish a model of disc degeneration induced by mechanical puncture combined with inflammatory factors.Four weeks after surgery,the pain threshold of rats was measured by the hot plate method for assessing the perception of heat injury in rats with intervertebral disc degeneration.MRI examination was performed to observe the disc degeneration in each group.ELISA was used to detect the levels of serum tumor necrosis factor α,interleukin 1β,interleukin 6 and prostaglandin E2.Hematoxylin-eosin and Safranin O-fast green staining were used to observe the morphological changes of the disc. RESULTS AND CONCLUSION:In terms of pain,the behavioral pain threshold of the experimental group was continuously decreased,and the levels of serum inflammatory factors were significantly higher compared with the control group.In terms of morphology,the MRI results showed that the L4-5 nucleus pulposus signal completely disappeared in the experimental group.Histopathological results showed that in the control group,the nucleus pulposus was intact,more notochord cells were visible,and some fiber rings were ruptured,while in the experimental group,there are fewer notochord cells and the structure of the nucleus pulposus and fibrous ring is disturbed,with the boundary disappearing.To conclude,mechanical puncture combined with tumor necrosis factor alpha and complete Freund's adjuvant can successfully establish a discogenic low back pain model in rats.This operation is simple and economical to achieve obvious disc degeneration and low back pain,with greatly shortened molding cycle.This model can be used as a reference for studying discogenic low back pain models.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*

Objective:To explore the optimum time of ambulation of atrial fibrillation patients after radiofrequency ablation, to provide basis for patients' early postoperative rehabilitation.Methods:By convenient sampling method, a total of 120 patients with atrial fibrillation after radiofrequency ablation were collected at Yanghu Branch and City Branch of Changzhou Second People's Hospital from January 2020 to May 2021. They were divided into the early group, middle group and late group according to the random number table method, each group were 40 cases. All patients received routine postoperative intervention, the time of ambulation were 4, 6 and 12 h after operation in the early group, middle group and late group, respectively. The complication rate within 24 h after operation was compared among the three groups, and the comfort level of the three groups at 24, 48 and 72 h after operation was evaluated with Comfort Status Scale (GCQ).Results:Finally, 111 patients were included, including 37 in the early group, 38 in the middle group and 36 in the late group. There was no significant difference in the incidence of bleeding or hematoma, urinary retention, lumbago within 24 h after operation among the three groups ( P>0.05). The incidence of postural hypotension within 24 h after operation in the early group was 2.7% (1/37), which was lower than 21.1% (7/38) and 25.0% (9/36) in the middle and late groups, with a statistically significant difference ( χ2=4.86, 7.67, both P<0.05). At 48 and 72 h after operation, the scores of physiological dimension, psychological dimension and the total score of GCQ in the early group were (20.68 ± 3.07), (22.54 ± 3.35), (81.68 ± 6.11) and (22.54 ± 3.73), (24.38 ± 2.49), (84.92 ± 6.37), higher than those in the middle group (19.16 ± 2.19), (21.32 ± 2.27), (78.24 ± 5.58), (20.93 ± 2.85), (22.32 ± 2.04), (81.66 ± 6.56), and those in the late group (18.44 ± 1.50) (21.31 ± 1.99), (78.06 ± 4.32), (20.89 ± 2.25), (21.58 ± 1.86), (80.28 ± 6.44), the differences were statistically significant ( t values were 2.19-4.15, all P<0.05). Conclusions:Ambulation at 4 h after operation does not increase peripheral vascular complications, but can reduce the incidence of postural hypotension and improve the comfort of patients with atrial fibrillation after radiofrequency ablation.

In order to meet the social demand for ultrasound talents, a layered training system of ultrasound medical talents suitable for China's national conditions has been explored. The department of ultrasound of West China Hospital of Sichuan University has formulated and implemented a "three-layers" ultrasound education and training system in combination with its own reality. The first layer mainly refers mastering the basic ultrasound examination ability mainly through relevant ultrasound theoretical knowledge and basic operation skills training. The second layer is based on the first level to further master the ability of ultrasound diagnosis and differential diagnosis of common and frequently occurring diseases in various systems, and to be capable of engaging in basic ultrasound teaching and scientific research. The third layer means mastering the ability of ultrasound diagnosis, evaluation and interventional diagnosis and treatment of difficult and specialized diseases, grasping the latest development direction of the sub-specialty, and having the ability to engage in ultrasound teaching and clinical research. The results show that the "three-layers" ultrasound education and training system conforms to China's national conditions and is worthy of reference and promotion.

Objective: To explore whether the pro-inflammatory effect of endoplasmic reticulum stress in placental tissues involves in the genesis of gestational diabetes mellitus (GDM). Methods: Forty gravidas who underwent regular prenatal examinations and delivered at Tongji Hospital were recruited from January to December, 2016. Among them, 20 were GDM women (GDM group), and the remaining twenty were served as the control, which were selected from those without GDM and matched for age and gestational weeks to the GDM group. Placental tissues were collected from the two groups. The ultrastructure of endoplasmic reticulum in trophoblast cells was observed under transmission electron microscope. The expression of glucose-regulated protein-78 (GRP-78), a marker protein for endoplasmic reticulum stress, and C/EBP homologous protein (CHOP) were detected using Western blotting. Five placental tissue samples were collected from normal gravidas for explant culture. Three subgroups were set up according to different culturing methods including culturing with IL-1β (5 ng/ml) for 20 h (IL-1β model group), 30 μmol/L thapsigargin (TG, an endoplasmic reticulum stress agonist) for 2 h after treating with IL-1β (5 ng/ml) for 18 h (IL-1β+TG intervention group) or with no stimulation (blank control group). Western blotting was used to detect the expressions of GRP-78, CHOP and glucose transporter 4 (GLUT4) in placenta explants. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by real-time fluorescence quantitative polymerase chain reaction (RT-PCR). Statistical analysis was performed using one-way analysis of variance, LSD and t test. Results: (1) In the GDM group, increased number and size of endoplasmic reticulum cisternae were observed in trophoblast cells. Moreover, obviously dilated endoplasmic reticulum and different size of fragments and vesicles were also seen under electron microscope. While the endoplasmic reticulum in the placental tissues of the control group showed no obvious swelling. (2) The expression of GRP-78 and CHOP protein in the GDM group were higher than those in the control group (0.90±0.17 vs 0.48±0.08, t=2.24; 0.85±0.13 vs 0.46±0.12, t=2.10; both P<0.05). (3) Compared with the blank control group, the expression of GRP-78 and CHOP protein in the IL-1β model group increased significantly (0.87±0.18 vs 0.36±0.07, t=2.67; 1.14±0.09 vs 0.78±0.06, t=3.20; both P<0.05); but the expression of GLUT4 protein significantly decreased (1.00±0.14 vs 2.21±0.49, t=2.40, P<0.05); the expressions of IL-6 and TNF-α mRNA significantly increased (0.89±0.23 vs 0.30±0.06, t=2.31; 0.62±0.16 vs 0.17±0.09, t=2.29; both P<0.05). Compared with the IL-1β model group, the expression of GRP-78 and CHOP protein significantly increased in IL-1β+TG group (2.02±0.32 vs 0.87±0.18, t=3.11; 2.18±0.31 vs 1.14±0.09, t=3.16; both P<0.05); the expression of GLUT4 protein significantly decreased (0.39±0.19 vs 1.00±0.14, t=2.66, P<0.05); the expression of IL-6 and TNF-α mRNA increased significantly (1.67±0.25 vs 0.89±0.23, t=2.26; 1.42±0.27 vs 0.62±0.16, t=2.51; both P<0.05). Conclusions Endoplasmic reticulum stress may be associated with increased release of pro-inflammatory cytokines in placental tissues of some GDM women and involved in the onset and development of GDM.

Objective:To establish the population pharmacokinetics model of mitiglinide given by oral route in Chinese healthy volunteers using nonlinear mixed effect model (NONMEM), investigate the pharmacokinetic characteristics of mitiglinide in Chinese healthy people to evaluate the factors that can influence the clinical pharmacokinetics of mitiglinide .Methods: Clinical data from 22 healthy volunteers were collected and the experiment was with single-dose administration.The volunteers were given 10 mg mitiglinide calcium orally and mitiglinide plasma concentration was determined by LC-MS/MS.The data was analyzed by the first order conditional estimation, and the influences of fixed effect factors such as demographic index and biochemical index were quantitatively evaluated . The population pharmacokinetics model of mitiglinide was established , and the result was verified by using the VPC and self-test meth-od.Results:The result showed that mitiglinide pharmacokinetics was fit single-compartment model .The inter-individual variability could be described by an exponential model .The typical values including central volume of distribution , clearance and absorption con-stant was 2.4 L· h-1(24％), 9.82 L(4％) and 6.46 h-1(14％), respectively.The clearance was influenced by creatinine clear-ance rate , and the absorption constant was influenced by ALT .Conclusion:The population pharmacokinetic parameters were mainly influenced by creatinine clearance rate and ALT .The established population pharmacokinetics model can explain the reasons for the in -dividual variation in the plasma concentration of mitiglinide , which can be used to guide the clinical administration of Chinese people .

BACKGROUND:Human amniotic epithelial cells have some properties of stem cells, which can be induced to differentiate into corneal epithelial cells, but cannot be tracedin vitro. OBJECTIVE:To investigate the feasibility and infection efficiency of adenovirus vector carrying enhanced green fluorescent protein (EGFP) into the human amniotic epithelial cells. METHODS:The adenovirus vectors carrying EGFP was transferred into human amniotic epithelial cells culturedin vitro. After cultured and amplified, the morphology difference between transfected and non-transfected human amniotic epithelial cels was observed. The transfected human amniotic epithelial cells were observed under fluorescence microscope, and the cell cycle and the expression rate of EGFP in transfected human amniotic epithelial cells were detected by flow cytometry. RESULTS AND CONCLUSION:No obvious difference in the cell morphology was found between transfected human amniotic epithelial cells and normal human amniotic epithelial cells cultured in vitro. Flow cytometry analysis revealed that the EGFP positive rate was highest and reached up to 99.01% at 48 hours after transient transfection. The cell cycle of human amniotic epithelial cells transfected by the adenovirus vector was slowed a bit. To conclude, the adenovirus vector is a good medium of transfecting EGFP into human amniotic epithelial cells, and makes it more convenient to observe the further transformation of human amniotic epithelial celsin vitro.

Tumor microenvironment (TME) plays a key role in the development and progression of tumors, such as pro?moting local drug resistance, immune escape, and distal metastasis. According to the TME of different individuals, accurate evaluation and selection of clinical medication can effectively control the malignant transformation of carcinoma in situ and metastatic cancer. At present, the main method to treat cancer is chemotherapy, TME can regulate the reaction of the tumor cells to the standard chemotherapy and target drug therapy, so the combination of the targeted TME therapy and chemothera?py will achieve better clinical efficacy. In this review, we summarized the mechanisms of TME in breast cancer, including ex?tracellular matrix, carcinoma-associated fibroblasts, carcinoma-associated macrophages, regulatory T cells and bone marrow mesenchymal stem cells, which providing a theoretical basis for the development of TME targeted therapy.

BACKGROUND:There is a lack of study on material properties and parameters of foot finite element models in China. Vernier caliper is a common method for measuring the width and thickness of ligaments and tendons to calculate the cross-sectional area.
OBJECTIVE:To design a new ligament cross-sectional area measuring instrument to improve the measurement accuracy.
METHODS:The cross-sectional area of the five fresh cadaver ankle ligaments was respectively measured using the new instrument and vernier caliper, and then a comparative analysis of the two measurement methods was performend.
RESULTS AND CONCLUSION:The cross-sectional area of anterior talofibular ligament, calcaneofibular ligament, tibionavicular ligament and calcaneotibial ligament was (20.61±7.52), (22.38±11. 49), (33.09±9.91) and (28.20±10.88) mm2, respectively measured by the vernier caliper, and (17.59±4.03), (20.77±7.91), (28.08±8.14) and (30.39±7.98) mm2 by the new ligament cross-sectional area measuring instrument. These results suggest that this new measuring instrument is accurate, reliable and easy to operate, which can be used as a special instrument to measure ligament cross-sectional area, but further studies wil be necessary.

Background and purpose: Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) can be used for magnetic resonance imaging systemic examination, especially in examing the metastatic lesions, lymph node and bone diseases, and the imaging result is similar with PET. This study aimed to evaluate the application value of magnetic resonance DWIBS and positron emission tomography with computed tomography (PET/CT) on malignant metastatic diseases. Methods: Thirty-six patients confirmed with malignant tumors accompanying metastasis by the pathology of operation or biopsy underwent both DWIBS imaging and PET/CT, chi-square test and Kappa test were used for comparing the detection results of metastasis by these 2 imaging methods. Results:Among the 36 malignant tumor patients with 238 metastatic lesions, 218 (91.6%, 218/238) lesions in DWIBS and 209 (87.8%, 209/238) lesions in PET/CT were detected, with 200 lesions detected by the two methods simultaneously, and the concordance rate was 88.7%(211/238);but there was no statistical signiifcance between this two methods (χ2=1.843, P=0.157). Kappa test showed a fair concordance rate between DWIBS and PET/CT (P=0.000).There were different significance between DWIBS and PET/CT in detecting metastatic lesions of brain and bone (P=0.005 and 0.031);But there was no signiifcant differences (P=0.309 and 1.000) in detecting metastatic lesions of lymph nodes and liver. Conclusion:DWIBS could detect metastatic lesions effectively, and there is ifne consistency with PET/CT. DWIBS is more sensitive than PET/CT in detecting metastatic lesions of brain and bone, so DWIBS could be chosed for screening metastatic lesions according to the characteristics of different primary tumors.