ObjectiveTo investigate the dynamic expression profiles and potential regulatory mechanisms of long non-coding RNAs （lncRNAs） in male reproductive system aging. MethodsA naturally aging C57BL/6 mouse model was used and 4 mice were selected each at 3， 15， and 21 months of age. RNA was extracted from seven regions of the male reproductive tract （testis， efferent duct， initial segment of epididymis， caput epididymis， corpus epididymis， cauda epididymis， and vas deferens）， followed by RNA sequencing and bioinformatics analysis. ResultsRegion-specific dynamic expression profiles of lncRNAs were constructed in the testis， epididymis （efferent duct， initial segment， caput， corpus， and cauda）， and vas deferens of male mice. Combined with gene functional enrichment analysis， the functional associations of lncRNAs were elucidated in reproductive system aging. The differentially expressed lncRNAs in the aging testis were primarily involved in hormone biosynthesis and extracellular matrix organization， while those in the initial segment of the epididymis were closely related to cell recognition and epithelial cell migration. A comprehensive lncRNA expression atlas associated with male reproductive aging was established. ConclusionLncRNAs may participate in male reproductive aging through the regulation of the reproductive microenvironment， which provides key molecular targets and a research foundation for understanding age-related fertility decline.

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

ObjectiveTo observe the efficacy and safety of Uyghur medicine Yangxin Dawayimixike Honey Paste （养心达瓦依米西克蜜膏， YDMHP） in the treatment of stable angina pectoris （SAP） of qi stagnation and blood stasis syndrome. MethodsA randomized ， double-blind， positive-controlled，multi-center clinical trial was conducted， in which 370 patients with SAP of qi stagnation and blood stasis syndrome were randomly divided into treatment group（279 cases）and control group（91cases）at a ratio of 3∶1. The treatment group was orally administered with YDMHP， 3 g each time， and placebo of Xuefu Zhuyu Capsule （血府逐瘀胶囊）， 2.4 g each time， while the control group was treated with Xuefu Zhuyu Capsule， 2.4 g each time， and placebo of YDMHP， 3 g each time， both twice a day for a course of 12 weeks. The primary outcome was the effect of angina pectoris symptom. The secondary outcomes include single angina symptom scores such as number of attacks， duration of attacks， pain intensity and usae of nitroglycerin scores， the total angina symptom score before and after the treatment， the usage of nitroglycerin， the exercise duration in treadmill exercise test （TET） and the Duck treadmill score among patients，the scores of Seattle Angina Questionnaire （SAQ） on five dimensions including physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception， and efficacy of TCM syndrome and of each single TCM symptom after treatment. The safety were evaluated by examine blood routine， urine routine， liver and kidney function， fasting blood sugar， electrocardiogram， adverse events. ResultsThe total effective rate of angina symptom in the treatment group was 71.69% （200/279）， significantly higher than 51.64% （47/91） in the control group （P＜0.01）. The curative and markedly effective rate of TCM syndrome in the treatment group was 53.05% （148/279）， which was significantly higher than 25.27% （23/91） in the control group （P＜0.01）. After treatment， scores of the number as well as duration of angina attacks and pain severity， the total score of angina symptoms， and the usage of nitroglycerin significantly decreased in both groups， and more changes were seen in the treatment group than in the control group； the scores of physical limitations， anginal stability， anginal frequency， treatment satisfaction， and disease perception in both groups significantly increased， and more improvement were shown in the experimental group regarding the anginal stability， anginal frequency and treatment satisfaction （P＜0.05 or P＜0.01）. The effects of chest pain， chest tightness， palpitation， shortness of breath and fatigue in experimental group were significantly higher than those in control group （P＜0.05 or P＜0.01）. There was no significant difference in the exercise duration of treadmill test and Duke score among patients between the two groups either before or after treatment （P＞0.05）. Adverse events occurred in 66 cases （23.66%） of the experimental group and 16 cases （17.58%） of the control group， with no statistical significance between the two groups （P＞0.05）. ConclusionThe Uyghur medicine YDMHP can effectively improve symptoms of angina pectoris， reduce the number， duration， and intensity of attacks， decrease the dosage of nitrogly-cerin and improve the individual TCM symptoms and has good safety in the treatment of SAP patients of qi stagnation and blood stasis.

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Objective To explore the key targets and signaling pathways in the therapeutic mechanism of Semiliquidambar cathayensis Chang(SC)root against pancreatic cancer network pharmacology and molecular docking studies and cell experiments.Methods The targets of SC and pancreatic cancer were predicted using the network pharmacological database,the protein-protein interaction network was constructed,and pathways,functional enrichment and molecular docking analyses were performed.CCK-8 assay was used to test the inhibitory effect of the aqueous extract of SC root on 8 cancer cell lines,and its effects on invasion,migration,proliferation,and apoptosis of pancreatic cancer cells were evaluated.Western blotting was performed to verify the results of network pharmacology analysis.Results We identified a total of 18 active components in SC,which regulated 21 potential key targets in pancreatic cancer.GO and KEGG pathway enrichment analyses showed that these targets were involved mainly in the biological processes including protein phosphorylation,signal transduction,and apoptosis and participated in cancer signaling and PI3K-Akt signaling pathways.Among the 8 cancer cell lines,The aqueous extract of SC root produced the most obvious inhibitory effect in pancreatic cancer cells,and significantly inhibited the invasion,migration,and proliferation and promoted apoptosis of pancreatic cancer Panc-1 cells(P<0.05).Western blotting confirmed that SC significantly inhibited the phosphorylation levels of PI3K and AKT in Panc-1 cells(P<0.001).Conclusion The therapeutic effect of SC root against pancreatic cancer effects is mediated by its multiple components that act on different targets and pathways including the PI3K-Akt pathway.

Objective:To investigate the pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual in infants and young children undergoing daytime surgery.Methods:One hundred and four pediatric patients of either sex, aged 3-36 months, of American Society of Anesthesiologists Physical Status classification Ⅱ, with body mass index of 18.5-28.0 kg/m 2, diagnosed with oblique inguinal hernia and/or hydrocele, scheduled for laparoscopic high ligation of hernia sac and/or high ligation of sphingoid surgery, were included in the study. Intraoperative neuromuscle relaxation was assessed by transdermal stimulation of the ulnar nerve in the wrist using a TOF Guard monitor. Rocuronium 0.9 mg/kg, propofol 3 mg/kg, and sufentanyl 0.5 μg/kg were intravenously injected for anesthesia induction, and propofol 6-8 mg·kg -1·h -1 was intravenously infused to maintain anesthesia. The pediatric patients were divided into Ⅰgroup and Ⅱ group according to the degree of postoperative neuromuscular block. In group Ⅰ, sugammadex 2 mg/kg was intravenously injected when TOF returned to T 2 recurrence. In group Ⅱ, sugammadex 4 mg/kg was intravenously injected when the single stimulation count was 1 or 2 after tetanic stimulation. At 2 and 10 min after rocuronium administration, at the end of operation, 2 and 10 min after sugammadex administration, and when the children met the standard of leaving the resuscitation room, venous blood samples were collected for determination of plasma concentrations of rocuronium and sugammadex using ultra-high performance liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined using the Pheonix WinNonlin software. The onset of rocuronium and time for recovery of TOF ratio to 90% were recorded. Results:The pharmacokinetics of sugammadex was fitted to the nonlinear mixed-effect satrioventricular model.There was no significant difference in the peak concentration, area under the drug concentration-time curve, elimination half-life, apparent clearance, apparent volume of distribution, mean retention time, and time for TOF ratio returning to 90% between the two groups ( P> 0.05). Conclusions:The pharmacokinetics of sugammadex in reversal of rocuronium-induced muscle relaxant residual is fitted to a nonlinear mixed-effect satrioventricular model, and sugammadex 2 and 4 mg/kg have similar pharmacokinetics in infants and young children undergoing daytime surgery.

OBJECTIVE To establish a physiologically-based pharmacokinetic （PBPK） model of amikacin in elderly patients with renal insufficiency. METHODS PK-SIM® software was adopted for model building， optimization and simulation. The physical and chemical properties and pharmacokinetic parameters related to amikacin were collected by literature review. The PBPK model on adults was established and extrapolated to the elderly population based on the built-in human model. Data from clinical PK studies were used to optimize and validate the model. The goodness of fit， relative residual， and mean folding error （MFE） were used to evaluate the performance of forecasting. The final model was employed to simulate the exposure of amikacin in the elderly population with renal insufficiency， and the efficacy and safety of commonly used clinical dosing regimens were evaluated， and the recommended regimens were proposed. RESULTS The established PBPK model of amikacin had good prediction performance in both adult and elderly populations， with the absolute mean of relative residual value of 25%； the MFE of peak concentration （cmax） and area under the plasma concentration curve （AUC0－∞） in all simulation occasions ranged ＞0.5-＜2. The simulation results showed that， compared with healthy adults， no significant clinical difference in cmax was observed in the elderly with renal insufficiency at the same dosing regimen， but the trough concentration increased significantly due to accumulation. Prolonging the administration interval of amikacin rather than reducing the dosage was more helpful to ensure the efficacy and to reduce the occurrence of nephrotoxicity. CONCLUSIONS The PBPK model for amikacin is successfully established in the elderly patient with renal insufficiency， and shows good predictive performance.

Objective:To analyze the molecular characteristics of Echovirus 11 (Echo11) strains isolated in Xiangyang, Hubei Province from 2016 to 2017 based on the sequences of VP1 gene.Methods:Rectal and throat swab specimens were collected from children with hand, foot and mouth disease (HFMD) in Xiangyang from 2016 to 2017. Echo11 strains were detected by real-time reverse transcriptase PCR (RT-PCR) and isolated after cultured in human rhabdosarcoma (RD) cells. The VP1 regions of Echo11 strains isolated from RD cells and the whole genomes of three representative Echo11 strains were amplified by conventional RT-PCR and the sequences were analyzed. DNAStar7.0 (MegAlign) and MEGA6.0 (Data) were used to analyze the homology and mutation sites in nucleotide and amino acid sequences. Neighbor-joining method was used to construct phylogenetic trees. Recombination analysis was performed with SimPlot software (BootScanning).Results:A total of 11 Echo11 strains were isolated from 3 494 HFMD cases, accounting for 0.31%. They were highly homologous in the VP1 gene. These strains shared 98.4%-100.0% homology in nucleotide sequences and 98.3%-100.0% homology in amino acid sequences. The homology between the 11 Echo11 strains and the prototype strain (Echo11/Gregory, X80059) was 73.9%-74.8% in nucleotide sequences and 87.7%-88.7% in amino acid sequences. All of the Echo11 strains circulating in Xiangyang were classified into lineage D, having a similarity to the strains circulating in some regions of mainland China since 2013. In multiple regions of the genome, the Echo11 strains isolated in Xiangyang were highly similar to the Henan Echo1 strains in 2010 and the Hubei Echo6 strains in 2015, suggesting there was recombination within the genome of Echo11 strains in Xiangyang.Conclusions:The Echo11 strains circulating in Xiangyang from 2016 to 2017 belonged to lineage D and were recombinant strains.

OBJECTIVE: To explore the correlation of different glucose metabolism statues with chronic kidney disease (CKD) in middle-aged and elderly individuals in Lanzhou. METHODS: Based on the baseline data of REACTION Study in Lanzhou area, we randomly sampled 10 038 residents aged 40-75 years in 3 communities in Lanzhou, who were classified into normal glucose tolerance (NGT), impaired glucose regulation (IGR) and diabetes groups. The estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) were used to assess the renal function and albuminuria, respectively. Binary logistic regression was performed to analyze the contribution of the risk factors to CKD. Polynominal regression was used to determine the trends of eGFR with the increment of ACR. RESULTS: Among all the participants, the prevalences of albuminuria, CKD and renal insufficiency (RI) were 26.2%, 27.4% and 2.5%, respectively. The prevalence of albuminuria, CKD and RI were significantly higher in the diabetes group than in IGR and NGT groups ( CONCLUSIONS Diabetes mellitus is a significant risk factor for albuminuria and RI, while IGR is not. Screening for albuminuria and eGFR is highly recommended for individuals with diabetes, hypertension, and obesity, especially in women and the elderly population.
Adult ; Aged ; Albuminuria/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Female ; Glomerular Filtration Rate ; Glucose ; Humans ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic/epidemiology* ; Risk Factors

OBJECTIVE： To analyze the current status and trend of opioids consumption in China， and to provide reference for rational use of opioids. METHODS： Purchasing data on five opioids as fentanyl， morphine， pethidine， oxycodone and hydromorphone， were extracted from the database of the Medicine Economic Information Network from 2014 to 2016. Drug consumption was measured by the daily dose per million population （unit： S-DDD）， and the consumption amount of all opioids and different dosage forms （including oral dosage form， injection and other form） in China and different districts were analyzed and compared. RESULTS： The consumption amount of five opioids increased from 69.62 S-DDD in 2014 to 78.64 S-DDD in 2016. The consumption amount of hydromorphone and oxycodone showed an upward trend， while the consumption amount of morphine was basically unchanged， and the consumption amount of fentanyl and pethidine showed a downward trend. The consumption amount of oral dosage form increased from 39.77 S-DDD in 2014 to 45.61 S-DDD in 2016， the consumption amount of the injection increased from 20.74 S-DDD in 2014 to 24.23 S-DDD in 2016， and the consumption amount of other form decreased from 9.11 S-DDD in 2014 to 8.81 S-DDD in 2016. The consumption amount of oral dosage form was around twice that of injection， with the gap expanding yearly. Regionally， the consumption amount of five opioids in the eastern region was the highest， followed by the western region， and the lowest but the highest growth rate in the central region from 2014 to 2016 （in 2016， consumption amount of eastern， western and central regions were 94.04， 67.90， 63.78 S-DDD， with increase rate of 8.50％， 11.77％， 16.17％， compared with 2014）. Morphine was the most widely used drug in all regions， followed by fentanyl； in the eastern and central regions， the use of oral and injection dosage form increased year by year； in western region， the use of oral dosage forms increased while that of injection decreased year by year. CONCLUSIONS： The opioids consumption in China is increasing overall， with regional differences. Nonetheless， the overall consumption is still low. On the premise of strict supervision， it is necessary to take measures to promote the rational use of opioids in different areas.