To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.
Action Potentials ; Arrhythmia/*etiology ; Heart Ventricles/metabolism ; Myocardial Infarction/complications ; Myocardial Infarction/metabolism ; Myocardial Infarction/*pathology ; Myocytes, Cardiac/*cytology ; Patch-Clamp Techniques ; Potassium Channels/*metabolism

AIM: To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), and to investigate the changes of action potential duration (APD),transient outward potassium current (I to ), delayed rectifier potassium current (I K) and inward rectifier potassium current (I K1 ) of left ventricular myocytes in noninfarcted zone of HMI. METHODS: 12 rabbits were randomly assigned in two groups: HMI group (thoracotomy and ligation of the circumflex coronary); sham-operated group (thoracotomy but no conorary ligation). 3 months after operation, whole cell patch clamp technique was used to record APD, I to , I K and I K1 of ventricular myocytes in non-infarcted zone. RESULTS: Membrane capacitance was larger in HMI group than that in sham-operated group. Action potential duration was lengthened significantly in HMI group and early after depolarization (EAD) appeared in HMI group. The densities of I to , I K,tail and I K1 were reduced significantly in HMI group (P

ObjectiveTo investigate the value of peripheral blood long non-coding RNA-LET (lncRNA-LET) in the diagnosis of chronic hepatitis B (CHB) cirrhosis, and to provide a basis for early clinical diagnosis and treatment of liver cirrhosis. MethodsA total of 175 CHB patients who attended The Affiliated Hospital of Chengde Medical University from March 2017 to May 2019 were enrolled, among whom 52 patients with hepatitis B cirrhosis were enrolled as cirrhosis group and 123 patients without the pathological changes of liver cirrhosis were enrolled as non-cirrhosis group. A total of 40 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as normal control group. Liver function parameters and the level of lncRNA-LET in peripheral blood were measured for all subjects. The t-test was used for comparison of continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H test was used for comparison of ranked data. A Pearson correlation analysis was performed to investigate correlation. The receiver operating characteristic (ROC) curve was used to investigate the value of peripheral blood lncRNA-LET in predicting liver cirrhosis. Results Compared with the normal control group, the cirrhosis group and the non-cirrhosis group had significantly higher serum levels of the liver function parameters total bilirubin (TBil), total bile acid (TBA), albumin (Alb), and alanine aminotransferase (ALT) (all P＜0.05) and a significantly lower serum level of cholinesterase (ChE) (P＜0.05); compared with the non-cirrhosis group, the cirrhosis group had significantly higher serum levels of TBil, TBA, Alb, and ALT (all P＜0.05) and a significantly lower serum level of ChE (P＜0.05). Compared with the normal control group, the cirrhosis group and the non-cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood (P＜0.05), and the cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood than the non-cirrhosis group (P＜0.05). The relative expression of lncRNA-LET decreased significantly with the increase in liver fibrosis stage (P＜0.05). In the patients with CHB, the relative expression of lncRNA-LET in peripheral blood was negatively correlated with liver fibrosis stage, TBil, TBA, Alb, and ALT (r=-0.352,-0.372,-0.364, and -0.410, all P＜0.001) and was positively correlated with ChE (r=0.340, P＜0.001). The ROC curve was used to analyze the value of peripheral blood lncRNA-LET in predicting liver cirrhosis, and the area under the ROC curve was 0934, with an optimal cut-off value of 0.833, a sensitivity of 84.57%, and a specificity of 80.57%. ConclusionThe expression level of lncRNA-LET in peripheral blood decreases with the progression of liver fibrosis and has a good value in the diagnosis of CHB cirrhosis, and therefore, it can be used as a potential biological indicator for the diagnosis of liver cirrhosis.

One of the primary purposes of the innovative development of ethnomedicines is to use their excellent safety and significant efficacy to serve a broader population.To achieve this purpose,modern scientific and technological means should be referenced,and relevant national laws and regulations as well as technical guides should be strictly followed to develop standards and to perform systemic research in producing ethnomedicines.Finally,ethnomedicines,which are applied to a limited extent in ethnic areas,can be transformed into safe,effective,and quality-controllable medical products to relieve the pain of more patients.The innovative development path of ethnomedicines includes the following three primary stages:resource study,standardized development research,and industrialization of the achievements and efforts for internationalization.The implementation of this path is always guaranteed by the research and development platform and the talent team.This article is based on the accumulation of long-term practice and is combined with the relevant disciplines,laws and regulations,and technical guidance from the research and development of ethnomedicines.The intention is to perform an in-depth analysis and explanation of the major research thinking,methods,contents,and technical paths involved in all stages of the innovative development path of ethnomedicines to provide useful references for the development of proper ethnomedicine use.

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.
Action Potentials ; Animals ; Arrhythmias, Cardiac ; etiology ; Female ; Heart Ventricles ; metabolism ; Male ; Myocardial Infarction ; complications ; metabolism ; pathology ; Myocytes, Cardiac ; cytology ; Patch-Clamp Techniques ; Potassium Channels ; metabolism ; Rabbits

Objective We investigated the correlation between inflammatory cytokines and drugresi-stant proteins. Methods Fourteen DBA1 mice were successfully induced by collagen and Freund's adjuvant. According to the scores of synovial pathology, the collagen-induced arthritis (CIA) group was divided into mild, moderate-severe groups, another four mice were selected as controls. The mRNA expressions of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance protein 1 (MRP1) in splenic lymphocyte cells were measured by reverse transcription-polymerase chain reaction (RT-PCR). The concentrations of inter-leukin (IL)-1β, IL-2, IL-6, IL-10, umor necrosis factor (TNF)-α, IL-17 in serum were detected by Cytometric Bead Array (CBA). The correlation between different inflammatory cytokines and these proteins were analyzed, then one of the proteins which were most related with cytokines by immunohisto-chemical (IHC) in the synovium was studied. Data were analyzed by the Mann-Whitney U test, Kruskal-Wallis H test and spearman analysis. Results ①Compared with normal controls, the levels of IL-6 and TNF-α in the serum of mild CIA group, moderate-severe CIA group were significantly increased {IL-6 controls: [7.75 (5.14, 9.17) pg/ml];mild CIA: [25.31 (15.15, 29.27) pg/ml]; modeate-severe CIA: [45.03 (38.87, 64.02) pg/ml]. TNF-α: controls: [22.81 (20.84, 28.17) pg/ml]; mild CIA: [45.00(32.76, 58.51) pg/ml]; modeate-severe CIA: [45.00(39.78, 8.95) pg/ml]}(Z=14.383, P<0.05; Z=8.375, P<0.05). Compared with the mild CIA group, the level of IL-6 in serum was significantly increased in the moderate-to-severe CIA group (P<0.05), but there was no signigicant difference in the TNF-α level (P>0.05). ② In the spleen lymphocytes, there was no significant difference in the mRNA expression level of P-gp and BCRP among the groups, but the mRNA expression level of MRP1 was significantly increased (Z=12.634, P<0.05). Compared with the mild CIA group, the MRP1 mRNA in the moderate-severe CIA group was higher, the difference was significant (Z=12.634, P<0.05). There was a correlation between mRNA expression of MRP1 and P-gp (r=0.635, P=0.015). ③ The mRNA expression of MRP1 was positively correlated with IL-6 level (r=0.711, P=0.004). ④ The expression of MRP1 in normal group, low-level IL-6 group and high- IL-6 level group were as follows: [1.08 (0.65, 1.30)], [1.32 (1.08, 1.49)], [2.07 (1.77, 2.22)] respectively.⑤Compared with the controls, the cytoplasm/membrane of the knee and ankle joint synovial tissue in the CIA group was yellowish-brown, which indicated that MRP1 expression was positive. Conclusion In the CIA arthritis model, synovial tissue lesion is not only related to inflammatory cytokines, but also related to MRP1 expression in the ATP-binding cassette (ABC) transport protein family, and it is proved that IL-6 is highly correlated to MRP1.

Objective To identify the aging effects on air-conducted sound (ACS) elicited ocular vestibular-evoked myogenic potential (oVEMP) and cervical vestibular-evoked myogenic potential (cVEMP) in normal Chinese population.Methods Nighty-seven normal subjects (194 ears) were recruited for conventional ACS-oVEMP and ACS-cVEMP examinations.The candidates'age were 4-83 years old (Ave.± SD,45.7 ± 19.3),41 male and 56 female,divided into 5 groups according to age.500 Hz short tone burst was employed for examinations.Thresholds were identified and the parameters of the responses to 100dB nHL were calculated and compared among groups.SPSS 13.0 software was used to analyze the date.Results As the age growing,the response rate for oVEMP decreased.It was recorded 100％ in both ≤ 10-year-old and 11-30-year-old groups,84.00％ in the 31-50-year-old group,48.15％ in the 51-70-year-old group and 15.00％ in the ＞70-year-old group; while that for cVEMP were 100％ in both-≤10-year-old group and 11-30-year-old group,82.00％ in the 31-50-year-old group,77.78％ in the 51-70-year-old group and 45.00％ in the ＞ 70-year-old group.The thresholds elevated and the amplitudes decreased in both examinations with the age growing.However,latencies and latency-intervals of both oVEMP and cVEMP examinations displayed minor difference among groups except that nI latency of oVEMP prolonged with age growing.Conclusions With the age growing,the otolithic end organ input pathways degenerate in normal subjects,as shown that ACS elicited oVEMP and cVEMP responsed less with higher threshold and smaller amplitude.The extremely low response rates of both VEMPs in the ＞70-year-old group in this study indicates that VEMPs can only provide limited diagnostic information among very old people in clinical practice.

Objective:To investigate the short-term effects of articular injection of hyaluronic acid combined with glucocorticoid in patients with knee osteoarthritis.Methods:From October 2017 to June 2018, a total of 188 patients diagnosed with knee osteoarthritis received parallel articular injection. There were 60 cases with mild knee osteoarthritis, 72 with moderate and 56 with severe according to the WOMAC knee functional score. There patients were divided into group rank Ⅰ48 cases, Ⅱ 49 cases, Ⅲ 45 cases, Ⅳ 46 cases according to the knee joint X-ray Kellgren-Lawrence classification. The unified treatment regimen was 2.5 ml Sodium Hyaluronate (SHA) injection for the first time, SHA 2.5 ml and compound betamethasone injection (CBI) 1 ml for the second week, and 2.5 ml of SHA for the third week. WOMAC score and Lequesne index were used to evaluate joint function before the first injection and after SHA and SHA+CBI injection. The improvement rate of Lequesne index ≥30% or improvement rate of WOMAC score ≥25% was regarded as effective treatment.Results:Lequesne index and WOMAC score decreased gradually in the mild, moderate and severe groups after 3 weeks of injection. Among these patients, the improvement rates of Lequesne index after SHA injection and SHA+CBI injection were 36.44%±8.46% and 49.26%±13.75% in the mild group, 23.09%±12.61% and 30.66%±14.95% in the moderate group, and 10.50%±8.78% and 11.07%±6.52% in the severe group. The improvement rate of WOMAC score in the mild group after SHA injection and after SHA+CBI injection was greater than 25%. After SHA injection, the improvement rate of WOMAC score was 13.06%±10.21% in the moderate group, and 27.49%±13.61% after SHA+CBI injection. Those in severe group were all less than 25%. Kendall's staub correlation analysis results showed that there was a strong positive correlation between WOMAC function score and X-ray Kellgren-Lawrence classification ( r=0.744, P<0.001). The Lequesne index and WOMAC scores of the Kellgren-Lawrence X-ray classification decreased gradually after 3 weeks of injection. The improvement rate of Lequesne index period in group rank Ⅰ after SHA and SHA+CBI injection was 36.64%±10.05% and 52.00%±8.19%, respectively. That for group rank Ⅱ was 32.05%±8.09% and 41.95%±10.53%, group rank Ⅲ 16.93%±10.34% and 27.77%±10.25%, group rank Ⅳ 7.52%±5.53% and 7.60%±6.66%. The improvement rate of WOMAC score period in group rank Ⅰ after SHA and SHA+CBI injection was 29.48%±11.77% and 42.59%±13.55%, respectively. That for group rank Ⅱ was 26.72%±10.21% and 30.49%±16.90%, group rank Ⅲ 13.78%±5.96% and 23.05%±9.52%, group rank Ⅳ 4.77%±3.80% and 4.27%±4.23%. Conclusion:For mild or X-ray classification Ⅰ, Ⅱ knee osteoarthritis patients, articular injection SHA or SHA+CBI are effective. Further, SHA+CBI is better than single injection of SHA. SHA+CBI injection was effective for moderate knee osteoarthritis patients. For severe or X-ray classification Ⅲ, Ⅳ patients, SHA or SHA+CBI injection at interval are invalid.

BACKGROUND:The research of dental stem cells in the fields of regenerative medicine and tissue engineering has been deepening,bringing hope for the repair of tooth-related tissues and the treatment of systemic diseases.However,there is a lack of systematic research and analysis on the biological characteristics of dental stem cells in different age groups. OBJECTIVE:To explore the biological characteristics of the human deciduous tooth and permanent tooth pulp stem cells cultured in umbilical cord blood platelet lysate to provide a reliable basis for human platelet lysates to replace fetal bovine serum. METHODS:The pulp tissues of deciduous teeth,juvenile permanent teeth and adult permanent teeth were taken out and cultured in DMEM/F-12 medium supplemented with 10%fetal bovine serum or different concentrations(5%,10%and 15%)of human platelet lysates.Cell proliferation in the four groups was detected by cytometry.The optimal concentration of human platelet lysates was selected for subsequent experiments.Under the optimal concentration of human platelet lysates,human deciduous tooth and juvenile and adult permanent tooth pulp stem cells were cultured in vitro.The cell growth status was observed under the microscope.The specific antigen on the cell surface was detected by flow cytometry.The cell proliferation ability was tested by the cell counting method and CCK-8 assay.The cell differentiation ability in vitro was observed by a three-line differentiation assay. RESULTS AND CONCLUSION:(1)The cell proliferation rate of the 10%human platelet lysate group was the highest.(2)In all three groups,fusiform fibrous cells grew and expanded from around the tissue block.There was no significant difference between deciduous teeth and juvenile permanent tooth cells,but the adult permanent tooth cells were larger than the deciduous and juvenile permanent tooth cells of the same generation.(3)The results of flow cytometry showed that deciduous teeth,juvenile permanent teeth and adult permanent teeth conformed to the phenotypic characteristics of mesenchymal stem cells.(4)The proliferative capacity of adult permanent dental pulp stem cells was significantly lower than those of deciduous teeth and juvenile permanent dental pulp stem cells(P<0.01).(5)mRNA expressions of osteoblast-related genes alkaline phosphatase and bone morphogenetic protein 2,lipoprotein lipase and peroxisome proliferator-activated receptor γ2,mRNA expressions of chondroblast related gene type II collagen α1 and cartilage oligomeric matrix protein in adult pulp stem cells of permanent teeth were significantly lower than those of deciduous teeth and juvenile permanent teeth pulp stem cells(P<0.01).(6)Compared with adult dental pulp stem cells,human deciduous teeth and juvenile permanent teeth dental pulp stem cells have the stronger proliferative capacity and multidirectional differentiation potential,and are more suitable for clinical research and disease treatment.

Objective To explore the clinical features and expression of PLA2R in renal tissue of children with idiopathic membranous nephropathy.Methods Retrospective study was performed in patients with membranous nephropathy diagnosed through renal biopsy and the follow-up time was at least half a year in Shanghai Children's Hospital from January 2010 to February 2017.We compared their clinicopathological and pathological findings of IMN.Indirect immunofluorescence assay was used to detect glomerular PLA2R expression.We analyzed the differences of clinical features between the PLA2R negative and positive groups.T test,rank-sum test and Fisher exact test were used.Results Eleven cases had hematuria and proteinuria,9 cases presented with nephrotic syndrome,and 2 cases showed isolated proteinuria.Of the 22 cases of children with IMN,16 patients had complete remission (complete remission rate was 72.8％),and 22 patients had partial remission.The renal functiou of all cases was normal and in all cases the estimated glomerular filtration rate was ＞ 90 ml/(min· 1.73m2).Of 22 cases with IMN,7 cases were PLA2R-positive in renal tissue and 15 cases were PLA2R-negative.The age of positive group(10 years old) was older than the negative group (6 years old)(Z=-2.483,P＜0.05) and the time of positive group (6 months) for urine protein to return to negative was longer than the negative group (2.5 months) through treatment.These differences were significantly different (Z=-2.072,P＜0.05).Conclusions Hematuria and proteinuria can be found in most children with idiopathic primary membranous nephropathy.Prednisone combined with immunosuppressant was effective.The positive rate of PLA2R in renal tissue of children with IMN was about 32％.The age of PLA2.R positive group was older than the negative group.And the time of urine protein turning to negative in positive group was longer than that in the negative group.