BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.

BACKGROUND:Exercise is an effective method for preventing and treating osteoporosis,but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE:To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats,and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS:A rat model of postmenopausal osteoporosis was established,and a 24-week moderate-intensity exercise was used for intervention.After the experiment,serum estradiol levels were measured by ELISA,and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT.The biomechanical indicators of the tibia were tested by a three-point bending test.Autophagosomes were observed by transmission electron microscopy.The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION:The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group(P＜0.01).The body mass of rats in each group increased,and the order was the ovariectomized group＞the ovariectomized+exercise group＞the sham-operation group＞the sham-operation+exercise group.The bone mineral density and bone mass of rats in all groups significantly increased(P＜0.01),but the increase in the ovariectomized group was significantly lower than that of the other groups,and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group.Compared with the sham-operation group,the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased(P＜0.01),while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased(P＜0.01).Compared with the ovariectomized+exercise group,the ovariectomized group showed significantly lower bone volume fraction,number of trabeculae,and bone mineral density of cancellous bone(P＜0.05),extremely significantly lower trabecular thickness(P＜0.01),and significantly higher mean trabecular pattern factor,trabecular separation,and structural model index(P＜0.01).Compared with the ovariectomized group,the LC3-Ⅱ/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group(P＜0.05).Compared with the sham-operation and ovariectomized groups,the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups,respectively.To conclude,moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels.

Objective:To explore the effects of whole-body fatigue on the balance and ankle proprioception during drop landing of individuals with functional ankle instability(FAI)by comparing the differences in balance and pro-prioception between the FAI group and the control group before and after fatigue. Method:A total of 31 participants with unilateral FAI and 31 healthy participants were included in this study.A static balance test,dynamic balance test,and ankle proprioception test were conducted before and after fa-tigue.Sway distance(D)of the center of pressure(COP),root mean square of the COP(RMS),95％confi-dence ellipse area of the COP movements(95％AREA),normalized reach distance,and the area under the curve(AUC)were calculated and analyzed. Result:Before whole-body fatigue,the static balance,dynamic balance,and ankle proprioception during drop landing in FAI group were significantly lower than those in control group.After whole-body fatigue,the static balance,dynamic balance,and ankle proprioception during drop landing in the FAI group and control group decreased significantly(P＜0.05),and the increase of D,RMS and 95％AREA in FAI group were significant-ly larger than those in control group(P＜0.05),and the decrease of normalized reach distance in the postero-medial and posterolateral directions and AUC were significantly larger than those in control group(P＜0.05). Conclusion:Whole-body fatigue reduced the static balance,dynamic balance,and ankle proprioception,and the reduction was larger in FAI individuals than in healthy individuals.Therefore,whole-body fatigue may in-crease the risk of recurrent ankle sprain by reducing posture control and proprioception in FAI individuals.

OBJECTIVE:To investigate the general regularity and characteristics of propylthiouracil (PTU)-associated small vasculitis (ASV),and to provide reference for rational drug use in the clinic. METHODS:ADR/ADE case reports of PTU-ASV published during 1990-2016 were retrieved. The data of 118 ADR cases were analyzed statistically. RESULTS:The incidence of PTU-ASV was higher in female and was highest in 18-59 age group. Drug dose of 87 patients were within 600 mg/d,and the inci-dence of PTU-ASV was the highest within 1-5 years after medication. Main clinical manifestations were renal and lung function in-jury. After drug withdrawal,59 patients received hormone therapy,and 30 patients received hormone combined immunosuppressive agent. Finally,115 patients were recovered and 3 patients died. CONCLUSIONS:In older to reduce or avoid the occurrence of ADR,it is necessary to regularly check antineutrophil cytoplasmic antibody related indexes and evaluate the symptoms of ADR.

OBJECTIVE:To excavate and evaluate the security alert signals of linezolid after marketing,and to provide refer-ence for rational drug use in clinic. METHODS:The reporting odds ratio(ROR)method was used to excavate the security alert signals from the adverse drug events(ADE)data in the OpenFDA platform of FDA during second quarter of 2004-2016. The low-er limit of 95%CI >1 was regarded as suggestive of ADE alert signal. RESULTS:A total of 6828534 reports were extracted, among which there were 7224 reports mainly induced by linezolid. Top 10 ADE reports were thrombocytopenia,drug interac-tion,thrombocytopenia,nausea,anaemia,serotonin syndrome,diarrhoea,pyrexia,drug ineffective,vomiting. After the detec-tion of top 200 ADE reports by ROR method,120 signals related to 18 system organ class(SOC)were identified. Top 5 ADE sig-nals in turn by SOC were medical examination,nervous system disorders,blood and lymphatic system disorders,metabolism and nutrition disorders,cardiac disorders. The high risk signals with clinical reference value included 42 cases of optic neuropathy (ROR=56.33),350 cases of serotonin syndrome(ROR=52.86),162 cases of lactic acidosis(ROR=18.30),31 cases of endo-carditis (ROR=15.38),566 cases of thrombocytopenia (ROR=14.29),122 cases of bone marrow failure (ROR=14.20),261 cases of panhematopenia (ROR=11.92),86 cases of disseminated intravascular coagulation (ROR=10.91),58 cases of toxic epidermal necrolysis(ROR=9.06),etc. As for ADE reports,male was slightly higher than female,and the patients in age group of ≥45 reported evidently more compared to younger age group. CONCLUSIONS:By detecting and evaluating alert signals of li-nezolid through OpenFDA platform,we could effectively lay the foundation for further research of pharmacovigilance.

BACKGROUND: Several studies have focused on the association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism; however, the results are conflicting. The effects of statins show significant variability between individuals. This meta-analysis aimed to investigate the effects of the SLCO1B1 c.521T>C polymorphism on the lipid-lowering effects of statins. METHODS: We systematically searched PubMed and Web of Science to screen relevant studies. Meta-analysis was performed to identify the association between SLCO1B1 c.521 polymorphisms and the lipid-lowering effects of statinson the basis of the standard mean difference (SMD) and 95% confidence intervals (CIs). Additionally, we checked for heterogeneity (I 2) among studies and evidence of publication bias. We obtained eight studies including 2,012 wild genotype (T/T) and 526 variant genotype (T/C and C/C) cases. RESULTS: No significant difference was observed in the lipid-lowering efficacy of statins between the wildand variant genotypes of SLCO1B1, with a pooled SMD of 0.03 (95% CI: -0.07-0.13). Furthermore, there was no significant effect in the meta-analyses of the variant heterozygote, homozygote, and Chinese populations. Subgroup meta-analysis indicated that the timerequired for the statin to take effectdid notsignificantly affect the association between lipid-lowering efficacy of statins and SLCO1B1 c.521T>C polymorphism. However, thewild genotype improved the lipid-lowering efficacy of simvastatin with a pooled SMD of -0.26 (95% CI: -0.47- -0.05). CONCLUSIONS: No significant association was detected between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism, with the exception of simvastatin.
Alleles ; Databases, Factual ; Genotype ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Hyperlipidemias/drug therapy/genetics ; Polymorphism, Single Nucleotide ; Solute Carrier Organic Anion Transporter Family Member 1b1/*genetics

BACKGROUND:Once lumbar degenerative diseases merge with lumbar spinal stenosis, lumbar instability and degenerative scoliosis, surgical therapy is required for corresponding clinical symptoms, and the usage of internal fixators cannot be inevitable. Osteoporosis is rather common in the elderly. Therefore, how to implant stable pedicle screw fixation system in serious osteoporosis patients wil be a big difficulty. In recent years, some studies have proven the biomechanical stability of polymethylmethacrylate augmentation of a cannulated and fenestrated pedicle screw in the vertebral body, so it becomes very hot in the spine surgery. OBJECTIVE: To explore the clinical efficacy of the use of polymethylmethacrylate augmentation of a cannulated and fenestrated pedicle screw fixation for the treatment of lumbar degenerative disease accompanied with osteoporosis. METHODS:Thirty-one patients with lumbar degenerative disease accompanied with osteoporosis from Jun 2008 to Jan 2013 were selected, including 11 males and 20 females with an average age of 73.5 years (range, 65-86 years). There were 14 cases of lumbar degenerative stenosis, 9 of lumbar intervertebral disc herniation combined with segmental instability, 6 of lumbar degenerative spondylolisthesis, and 2 of lumbar degenerative scoliosis. The patients were treated with lumbar canal decompression, fusion and polymethylmethacrylate augmentation of a cannulated and fenestrated pedicle screw fixation according to their clinical features and imaging data. Visual analog scale for pain evaluation was used before and after fixation, the Japanese Orthopaedic Association (JOA) scale was used for assessment of neurological function and life skils before internal fixation and during folow-up. RESULTS AND CONCLUSION:Al cases were folowed up for 40 months (range, 36-48months). No screw breakage, rod breakage, screw extraction, loosening, pseudoarticulation formation, or incision infection was found. The postoperative visual analog scale score and the JOA score was remarkably improved (P < 0.05). For patients suffering from lumbar degenerative disease accompanied with osteoporosis, polymethylmethacrylate augmentation of a cannulated and fenestrated pedicle screw fixation is helpful for increasing the stabilization of screw and preventing from loosening and dislocation of the screws, and thereby beneficial for improvement and maintenance of clinical efficacy.

ObjectiveTo analyze the relationship between pancreatic cancer (PC) and diabetes mellitus (DM),and the clinical and pathological features of pancreatic cancer in patients with DM.MethodsFrom January,2008 to December,2010,151 patients with PC and 195 comparable patients without PC were enrolled in a case-control study to analyze the relationship between PC and DM.ResultsThe OR was 5.91 (95％ CI 3.03-8.00,P＜0.05) in PC patients with DM for less than 2 years,and 1.308 (95％ CI 0.37-4.60,P＞0.05) in patients with DM for 2 to 5 years,and 1.16(95％ CI 0.44-3.19,P＞0.05) for patients with DM for more than 5 years.There was no significant difference between PC patients with and without DM in gender,age,body-mass index (BMD,obstructive jaundice,tumour location and tumour metastases (P＞0.05).ConclusionsThere was a significant correlation between PC and DM.De novo DM may be a clinical manifestation in patients with PC.PC patients with concurrent DM have no particular clinical and pathological features.

BACKGROUND: The most commonly used rod-screw posterior spinal fixation system has some biomechanical drawbacks. The screw-plate system is more preferred for patients.OBJECTIVE: To prepare a new posterior spinal fixation system based on imaging results of distance between two pedicles,radian of spine flexion, extension and the height of intervertebral space of Chinese population.METHODS: The thoracolumbar data of 129 normal people were measured. According to the imaging measurements and relative documents, a device of gear-distraction plate (GDP) for spine reduction and fixation was designed. Eighteen fresh calf lumbar specimens were randomly divided into 3 groups, the test group was fixed by GDP and the other groups were fixed by CD and Steffee plate, respectively. The results of the displacement, strain, strength, stiffness and ultimate strength were measured under the states of vertical compression, flexion, extension and lateral bending respectively, and the results were statistically analyzed.RESULTS AND CONCLUSION: GDP could meet the need of strength and stiffness of human bodies. It showed superior to the CD and Steffee plate groups in strength and stiffness (P ＜ 0.05), with 13% or 14% torsion intensity greater than that of the CD or Steffee plate groups. The ultimate mechanical performance test showed that, the load bearing of the GDP group was greater than that of the CD and Steffee plate groups (P ＜ 0.05). The findings demonstrated that GDP for Chinese human presented with good biomechanical stability, which can promote vertebrae fracture union and prevent kyphosis relapses or vertebral height loses.

BACKGROUND: Amnion has been widely used in ophthalmology. Numerous studies have suggested that amnion transplantation did not induce acute immunologic rejection. These indicated that amnion transplantation can be used as a safe material for repair of dural defects.OBJECTIVE: To study the probability of freeze-dried amniotic membrane (FDAM) as a dural substitue. METHODS: Each of the guinea pigs underwent bilateral parietal craniectomy behind the coronal suture and beside the midline to expose the dura. On the right side, a piece of dura mater was removed. The dural defect was covered with a piece of FDAM. The exposed dura on the left was cut and sutured itself as control. The animals in each group were sacrificed at 15, 30, 60 and 90 days after operation, respectively. The implants were harvested and stained with hematoxylin-eosin, and histologically analyzed. RESULTS AND CONCLUSION: After operation, the behavior of all guinea pigs remained completely normal. The wound healing was achieved in all cases. No wound infection, subcutaneous effusion or cerebrospinal fluid (CSF) leakage occurred. The graft was degraded gradually and covered with a sheet of connective tissue. Dural defects repaired with FDAM showed no adhesions to the brain surface. 15 days after operation, plenty of scattered fibroblasts appeared in the dural substitute. 30 days alter dural graft implantation, parts of the implant disappeared; meanwhile the hyperplasia of fibrous connective tissue took place in the center part of the dural substitute, without the infiltration of inflammatory cells. 60 days after implantation, a majority of the dural graft was degraded, substituted by fibrous connective tissue which was of hyperplasia and low-grade degeneration, surrounded by a small quantity of giant cells. 90 days after operation, colloidal degeneration happened in the dural substitute, surrounded by ossification tissue and the degenerated fibrous connective tissue. The inflammatory cells were not discovered. The animal experiment proves FDAM to be a safe and applicable dural substitute.