Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

The blood-brain barrier (BBB) plays a crucial role in maintaining the homeostasis of the brain's internal environment, which poses challenges to the treatment of central nervous system diseases. Drug carriers can aid in the delivery of therapeutic agents across the BBB to exert their pharmacological effects. The article reviewed the pathways for drug delivery across the BBB, the intracerebral fate and the classification of drug carriers and focuses on the functions and characteristics of liposomes, exosomes, apoptotic bodies, cell-penetrating peptides, and cell-targeting peptides. The review will provide an outlook on the future and challenge of research in the field of drug delivery across the BBB.

Objective To explore the effect of microRNA-22-3p (miR-22-3p) regulating the expression of Kruppel-like factor 6 (KLF6) on the cardiomyocyte-like differentiation of bone marrow mesenchymal stem cell (BMSC). Methods Rat BMSC was isolated and cultured,and the third-generation BMSC was divided into a control group,a 5-azacytidine(5-AZA)group,a mimics-NC group,a miR-22-3p mimics group,a miR-22-3p mimics+pcDNA group,and a miR-22-3p mimics+pcDNA-KLF6 group.Real-time fluorescent quantitative PCR (qRT-PCR) was carried out to determine the expression of miR-22-3p and KLF6 in cells.Immunofluorescence staining was employed to detect the expression of Desmin,cardiac troponin T (cTnT),and connexin 43 (Cx43).Western blotting was employed to determine the protein levels of cTnT,Cx43,Desmin,and KLF6,and flow cytometry to detect the apoptosis of BMSC.The targeting relationship between miR-22-3p and KLF6 was analyzed by dual luciferase reporter gene assay. Results Compared with the control group,5-AZA up-regulated the expression of miR-22-3p (q=7.971,P<0.001),Desmin (q=7.876,P<0.001),cTnT (q=10.272,P<0.001),and Cx43 (q=6.256,P<0.001),increased the apoptosis rate of BMSC (q=12.708,P<0.001),and down-regulated the mRNA (q=20.850,P<0.001) and protein (q=11.080,P<0.001) levels of KLF6.Compared with the 5-AZA group and the mimics-NC group,miR-22-3p mimics up-regulated the expression of miR-22-3p (q=3.591,P<0.001;q=11.650,P<0.001),Desmin (q=5.975,P<0.001;q=13.579,P<0.001),cTnT (q=7.133,P<0.001;q=17.548,P<0.001),and Cx43 (q=4.571,P=0.037;q=11.068,P<0.001),and down-regulated the mRNA (q=7.384,P<0.001;q=28.234,P<0.001) and protein (q=4.594,P=0.036;q=15.945,P<0.001) levels of KLF6.The apoptosis rate of miR-22-3p mimics group was lower than that of 5-AZA group (q=8.216,P<0.001).Compared with the miR-22-3p mimics+pcDNA group,miR-22-3p mimics+pcDNA-KLF6 up-regulated the mRNA(q=23.891,P<0.001) and protein(q=13.378,P<0.001)levels of KLF6,down-regulated the expression of Desmin (q=9.505,P<0.001),cTnT (q=10.985,P<0.001),and Cx43 (q=8.301,P<0.001),and increased the apoptosis rate (q=4.713,P=0.029).The dual luciferase reporter gene experiment demonstrated that KLF6 was a potential target gene of miR-22-3p. Conclusion MiR-22-3p promotes cardiomyocyte-like differentiation of BMSC by inhibiting the expression of KLF6.
Animals ; Rats ; Myocytes, Cardiac ; Kruppel-Like Factor 6 ; Connexin 43 ; Desmin ; Cell Differentiation ; Azacitidine/pharmacology* ; Mesenchymal Stem Cells ; RNA, Messenger ; MicroRNAs

Objective: To compare and analyze the effect of repairing small skin and soft tissue defect wounds in functional areas of children with full-thickness skin grafts from different sites of abdomen. Methods: A prospective randomized controlled study was conducted. From January 2019 to June 2020, 60 female children with small skin and soft tissue defects in functional areas requiring full-thickness skin grafting, who met the inclusion criteria, were admitted to the First Affiliated Hospital of Air Force Medical University. According to the random number table, the children were divided into two groups, with 28 cases left in lateral abdomen group aged 5 (3, 8) years and 29 cases in lower abdomen group aged 5 (3, 7) years after the exclusion of several dropped-out children in follow-up. In lower abdomen group, 20 (12, 26) cm² wounds of children were repaired with (24±10) cm² full-thickness skin graft from transverse skin lines in the inferior abdomen area, while in lateral abdomen group, 23 (16, 32) cm² wounds of children were repaired with (24±9) cm² full-thickness skin graft from below the umbilical plane to above the groin in the lateral abdomen area. All the children were treated with continuous intradermal suture at the donor site incision and received continuous negative pressure treatment of -10.64 to -6.65 kPa in the donor and recipient areas after operation. The donor site was treated with a medical skin tension-reducing closure device since post-surgery day (PSD) 7. The use of medical skin tension-reducing closure device at the donor site, postoperative complications and suture removal time of the donor area were recorded, and the incidence of complications was calculated. On PSD 7, a self-designed efficacy satisfaction questionnaire was used to investigate the parents' satisfaction with the curative effect of their children. In post-surgery month (PSM) 1 and 6, Vancouver scar scale (VSS) was used to evaluate the scar at the donor site, and the VSS score difference between the two time points was calculated; the scar width at the donor site was measured with a ruler, and the scar width difference between the two time points was calculated. Data were statistically analyzed with independent sample t test or Cochran & Cox approximate t test, Mann-Whitney U test, and Fisher's exact probability test. Results: The proportion of children in lateral abdomen group who used the medical skin tension-reducing closure device in the donor area for equal to or more than 4 weeks after surgery was significantly higher than that in lower abdomen group (P<0.05). On PSD 7, there was one case of partial incision dehiscence in the donor area, one case of peripheral skin redness and swelling in the donor area, and one case of fat liquefaction in the donor area in lateral abdomen group, and one case of partial incision dehiscence in the donor area in lower abdomen group. The incidence of postoperative complications at the donor site of children in lower abdomen group was significantly lower than that in lateral abdomen group (P<0.05). Compared with that in lateral abdomen group, the suture removal time at the donor site of children after surgery in lower abdomen group was significantly shorter (t'=17.23, P<0.01). On PSD 7, the satisfaction score of parents with the curative effect of their children in lower abdomen group was significantly higher than that in lateral abdomen group (t'=20.14, P<0.01). In PSM 1 and 6, the VSS scores of scar at the donor site of children in lower abdomen group were 2.7±0.9 and 2.8±1.0, respectively, which were significantly lower than 7.1±2.2 and 9.1±2.7 in lateral abdomen group (with t values of 10.00 and 11.15, respectively, P<0.01). In PSM 6, the VSS score of scar at the donor site of children in lateral abdomen group was significantly higher than that in PSM 1 (t=3.10, P<0.01), while the VSS score of scar at the donor site of children in lower abdomen group was not significantly higher than that in PSM 1 (P>0.05). The VSS score difference of scar at the donor site of children in lateral abdomen group was significantly greater than that in lower abdomen group (Z=-8.12, P<0.01). In PSM 1 and 6, the scar widths at the donor site of children in lower abdomen group were 2.0 (1.0, 2.0) and 2.0 (2.0, 3.0) mm, respectively, which were significantly narrower than 6.0 (4.0, 10.0) and 8.5 (5.0, 12.0) mm in lateral abdomen group (with Z values of -13.41 and -14.70, respectively, P<0.01). In PSM 6, the scar width at the donor site of children in lateral abdomen group was significantly wider than that in PSM 1 (Z=-2.79, P<0.01), while the scar width at the donor site of children in lower abdomen group was not significantly wider than that in PSM 1 (P>0.05). The difference of scar width at the donor site of children in lateral abdomen group was significantly greater than that in lower abdomen group (Z=-14.93, P<0.01). Conclusions: The use of full-thickness skin grafts from the lower abdomen to repair small skin and soft tissue defect wounds in functional areas of children, especially girls, is effective, simple and easy to operate, and conforms to the principle of aesthetic repair. Compared with transplantation with full-thickness skin graft from the lateral abdomen, lower abdominal full-thickness skin grafting has a low incidence of donor site complications and no obvious scar hyperplasia, which is worthy of clinical promotion.
Abdominal Cavity/surgery* ; Child ; Cicatrix/surgery* ; Female ; Humans ; Postoperative Complications/surgery* ; Prospective Studies ; Skin Transplantation ; Wound Healing

Cardiology ; China ; Consensus ; Heart Failure/therapy* ; Humans ; Self-Management ; United States

Circadian rhythm disorder is a common society issue caused by jet lag,shift work,sleep disruption and changes in food consumption. Light is the major factor affecting the circadian rhythm system. Disruption of the circadian rhythm system can cause damage to the body,leading to some diseases. Maintaining a normal circadian system is of great importance for good health. Ideal therapeutic effect can not only alleviate symptoms of the diseases,but also recovery the disturbed circadian rhythm to normal. The paper summarizes the modeling methods of animal circadian rhythm disorder,diseases of circadian rhythm abnormality,regulation of circadian clock genes and medicine which are related to circadian rhythm to diseases of circadian rhythm disorder.
Animals ; Circadian Rhythm/genetics* ; Humans ; Jet Lag Syndrome/genetics* ; Sleep ; Sleep Disorders, Circadian Rhythm

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (

OBJECTIVE: To investigate the surgical choice of posterior osteotomy way by the observation of clinical outcome of Smith-Petersen osteotomy (SPO), pedicle subtraction osteotomy (PSO) and vertebral column re-section (VCR) for senile osteoporotic thoracolumbar fracture with kyphosis. METHODS: From June 2015 to August 2017, an amount of 8 elderly patients with thoracolumbar kyphosis caused by osteoporotic vertebral fracture underwent osteotomy approach for posterior osteotomy. All patients were old osteoporotic vertebral fracture more than 6 months and received invalid conservative treatment for 3 months including nonsteroidal anti-inflammatory and analgesic drugs, anti-osteoporosis drugs and acupuncture, etc. There were 3 males and 5 females, with an average age of 73.4 years (66 to 83 years), with an average course of the disease of 34.6 months (8 to 60 months). Eight patients had a total of 8 vertebral fractures, and fracture segment was in T of 1 case, T of 1 case, T of 3 cases, L of 2 cases, L of 1 case. Eight patients showed kyphosis caused by wedge deformation of single segmental vertebral fractures. The thoracolumbar kyphosis and symptoms were progressively developing into central sagittal imbalance. SPO osteotomy was performed in 3 cases, PSO osteotomy in 3 cases, and VCR osteotomy in 2 cases. Orthopaedic effects were analyzed by imaging measurements, including pre- and post-operative kyphosis Cobb angle, localized kyphosis (LK), thoracic kyphosis (TK), lumbar lordosis (LL), sacral tilt angle (ST) and sagittal vertical axis (SVA). Visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the pain and lumbar function. RESULTS: All the eight patients were followed up from 8 to 24 months with an average of 13.5 months and all the symptoms of low back pain have significantly reduced or disappeared. The VAS score decreased from 5-8 points (mean 6.5 points) before surgery to 1-4 points (mean 1.88 points) at the final follow-up, and the score was significantly improved. The ODI score decreased from 36-78 points (mean 60.25 points) before surgery to 10-32 points (mean 20.38 points) at the final follow-up, and the functional score improved significantly. During the follow-up period, X-ray examination showed that some patients had a slight decrease in the height of the intervertebral fusion, and the bone graft was healed. There was no obvious corrected degree loss and internal fixation loosening, and the thoracolumbar kyphosis was significantly improved. The mean Cobb angle of T-L was reduced from 25.3° to 2.8° with corrected rate of 89.3% ; LK was reduced from 43.4° to 7.1° with corrected rate of 86.2% ; TK was reduced from 49.9° to 30.6°, LL was reduced from 43.6° to 30.8°, and ST was changed from 24.0° to 32.1°, SVA was changed from 6.23 cm to 2.40 cm. CONCLUSION For the different pathological features and deformities of senile osteoporotic thoracolumbar fracture combined with kyphosis, SPO, PSO or VCR can achieve good orthopedic effect and clinical efficacy.

OBJECTIVE Vascular dementia (VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia. 2-Vessels occlusion (2-VO) has been widely used as a model of VD. Xiao-Xu-Ming decoction, a well-known traditional Chinese medicine prescrip-tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats. METHODS After XXM treatment, rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody. Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics. RESULTS XXM significantly alleviated 2-VO-induced learning and memory deficits, motor ability dysfunction, and neuronal plasticity injury in rats. The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process, etc. The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system. CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.

Objective To study the effect of clarithromycin on the phar-macokinetics of bicalutamide in rabbits .Methods Six New Zealand white rabbits were randomly divided into control group and test group , with 3 rabbits in each group.The control group was given bicalutamide 50 mg by gavage.The test group was given bicalutamide 50 mg +cla-rithromycin 250 mg by gavage , and blood samples were collected at di-fferent time points.After 3 weeks, a crossover test was performed.Bi-calutamide plasma concentration was detected by HPLC .The pharmacoki-netic parameters of bicalutamide were calculated using DAS 2.0 softwareand statistical analysis was performed using SPSS 20.0 software.Results The AUC0-∞of the test and control groups were ( 217.57 ±60.74 ) and (175.39 ±16.64) mg· L-1· h, MRT0-∞were ( 65.76 ±4.81 ) and (62.82 ±3.09)h, t1/2were (53.14 ±9.02) and (48.67 ±5.51) h, Cmax were ( 3.47 ±1.14 ) and ( 2.85 ±0.34 ) mg · L-1, CL/F were (0.24 ±0.05)and (0.29 ±0.03)L· h-1.AUC0-∞, t1/2, and Cmaxwere not statistically different (all P>0.05).MRT0-∞and CL/F were statistically significant (all P<0.05).Conclusion Clarithromycin reduces the clearance rate of bicalutamide in rabbits and prolongs the average residence time.