ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

Objective To understand the cognition status of high-alert medications among medical staffs in Chongming District of Shanghai,and to explore its influencing factors and improvement countermeasures,so as to provide references for safe clinical use and effective control of such drugs.Methods Convenient sampling method was used to investigate among medical staffs in 9 hospitals in Chongming District from March to May 2022,the survey content included general information of medical staff and their awareness of high-alert medications.The orderly multi-classification logistic regression was used to analyze the influencing factors of the cognition of high-alert medications among medical staffs.Results A total of 605 valid questionnaires were collected,including 263 from doctors and 342 from nurses.The results of univariate analysis showed that there were significant differences in the grade distribution of high-alert medications management knowledge scores among doctors of different gender,education background and whether to partcipate in in-hospital training(P＜0.05).There were significant differences in the grade distribution of high-alert medications management knowledge scores among nurses with different education background,hospital level and whether to partcipate in in-hospital training(P＜0.05).There was significant differences in the grade distribution of high-alert medications pharmacy knowledge scores whether doctors participated in in-hospital training(P＜0.05).There were significant differences in the grade distribution of high-alert medications pharmacy knowledge scores among nurses with different education background,professional title,working years and whether to partcipate in in-hospital training(P＜0.05).The results of multi-factor Logistic analysis showed that whether doctors had participated in in-hospital training was an influential factor for and high-alert medications management knowledge score level(OR=0.003,95％CI 0.000 to 0.023,P＜0.001),high-alert medications pharmacy knowledge score level(OR=0.252,95％CI 0.147 to 0.431,P＜0.001).Whether nurses participated in in-hospital training(OR=0.022,95％CI 0.010 to 0.048,P＜0.001)and hospital level(OR=3.353,95％CI 1.639 to 6.855,P=0.001)were the influencing factors of nurses'high-alert medications management knowledge score level,and education background(OR=4.933,95％CI 1.452 to 16.760,P=0.011)and whether nurses participated in in-hospital training(OR=0.414,95％CI 0.239 to 0.717,P=0.002)were the influencing factors of nurses'high-alert medications pharmacy knowledge score level.Conclusion The cognition of high-alert medications among medical staffs in Chongming District is at a medium level on the whole.It is suggested to improve their cognitive ability and risk prevention awareness by improving their education,strengthening the knowledge education and training of high-alert medications,and homogenizing management,so as to ensure the safety of clinical drugs.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

ObjectiveTo explore the imbalance of paravertebral muscle group for patients with unilateral lumbar disc herniation. MethodsFrom January, 2022 to January, 2023, 30 patients with unilateral lumbar disc herniation (observation group) and 30 healthy people matching in general data (control group) were measured the tension and stiffness of multifidus and erector spinae with MyotonPRO, while the observation group was assessed with Visual Analogue Scale (VAS) for pain and Japanese Orthopaedic Association (JOA) score, and the time of disease was also recorded. ResultsThe mean of bilateral tension and hardness of multifidus and erector spinae was more in the observation group than in the control group (|t| > 5.407, P < 0.001), and the tension and hardness of multifidus and erector spinae of the affected side were more than those of the unaffected side in the observation group (|t| > 11.219, P < 0.001). The tension and hardness of multifidus and erector spinae of the affected side were positively correlated with VAS score (r > 0.942, P < 0.001), and negatively correlated with JOA score (|r| > 0.886, P < 0.001). ConclusionThe tension and hardness of multifidus and erector spinae of the affected side increase after unilateral lumbar disc herniation, resulting in asymmetry.

ObjectiveTo evaluate the inter-rater and test-retest reliability of echo intensity of ultrasound image for quality of quadriceps femoris in patients with knee osteoarthritis (KOA). MethodsFrom March to December, 2021, 33 patients with unilateral KOA in Guangdong Provincial Second Hospital of Traditional Chinese Medicine were included. Ultrasound was used to observe the cross sections of rectus femoris (RF), vastus medialis (VM) and vastus lateralis (VL), and the images were saved. Two independent raters analyzed the average gray value of the picture with the Image J. One of the raters repeated the measurement. The intra-class correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC) and coefficient of variation (CV) were calculated and the Bland-Altman charts were drawn. ResultsThe gray value was higher in the RF, VM and VL in the affected side than in the healthy side (t > 2.262, P < 0.05). The inter-rater reliability was excellent, with ICC 0.982 to 0.995, SEM 1.60 to 3.82, CV 1.49% to 5.90%, and MDC value 4.43 to 10.59. The test-retest reliability of the rater was excellent, with ICC 0.969 to 0.990, SEM 2.37 to 5.41, CV 2.22% to 4.84%, and MDC value 6.57 to 15.00. Bland-Altman charts analysis showed that the consistency was good. ConclusionThe quadriceps femoris muscle quality is different between the affected and the healthy sides in patients with unilateral KOA. It is reliable to evaluate muscle echo intensity by Image J.

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.
Mitophagy ; Taurine ; Macrophages/metabolism* ; Protein Kinases/metabolism* ; RNA, Messenger

ObjectiveTo test the inter-tester reliability and test-retest reliability of MyotonPRO for evaluating neck and shoulder muscle performance parameters in patients with unilateral chronic neck pain, observe the difference of muscle performance between the healthy and affected sides of patients with chronic neck pain, and analyze the factors that cause the imbalance of muscle performance in patients with chronic neck pain. MethodsFrom January to June, 2023, 32 patients with unilateral chronic neck pain in Guangdong Second Traditional Chinese Medicine Hospital were selected. Two testers used the same MyotonPRO equipment to measure the muscle tone, muscle hardness and muscle elasticity on both sides of the sternocleidomastoid muscle and the upper trapezius muscle in the relaxed position. Tester 1 repeated the measurement after an interval of 30 minutes, and Tester 2 was measured within the time interval between the two measurements of Tester 1. The intraclass correlation coefficient (ICC), standard error of mean (SEM) and minimum detectable change (MDC) were calculated simultaneously. The measurement results were plotted into Bland-Altman diagram and systematic bias analysis was performed. The difference in muscle characteristics between the affected side and the healthy side was compared. At the same time, the Visual Analogue Scale (VAS) score and body mass index (BMI) of the subjects were collected for correlation analysis. ResultsExcept the sternocleidomastoid muscle elasticity of the affected side (ICC = 0.697), the inter-tester reliability of all other parameters was high to very high (ICC = 0.719 to 0.952, SEM = 0.04 to 6.53, MDC = 0.12 to 18.11). The test-retest reliability of all parameters was high (ICC = 0.883 to 0.981, SEM = 0.03 to 5.72, MDC = 0.09 to 15.84). Bland-Altman plot analysis showed that the scatter distribution was consistent. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle were higher on the affected side than on the healthy side (t > 2.846, P < 0.05). The asymmetry index of tension, hardness and elasticity of upper trapezius muscle and sternocleidomastoid muscle was significantly positively correlated with VAS score and BMI (r > 0.385, P < 0.05). ConclusionMyotonPRO has good inter-tester reliability and retest reliability in evaluating the muscle performance of both sides of patients with chronic neck pain. The muscle tone, muscle hardness and muscle elasticity of sternocleidomastoid muscle and upper trapezius muscle on the affected side were higher than on the healthy side, and the difference of muscle performance was positively correlated with pain and BMI.

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.

Background In view of circulatory diseases, most previous studies focused on the impacts of air pollution and meteorological factors, while ignoring the influence of built environment. Objective To investigate and quantify the impact of built environment on circulatory diseases in China. Methods Circulatory disease mortality data and built environment data (including urban greenery coverage, urban land use, urban land use mix, urban road facilities and urban medical facilities) of 17 cities in China from 2000 to 2019 were collected. Multiple linear regression was used to analyze which built environment elements had significant influence on circulatory diseases, and to quantify their effects. Furthermore, the changes of built environment indicators on circulatory disease mortality were evaluated under different levels of urban economic development and various air quality. Results The built environment affected the mortality of circulatory diseases during the study period (P<0.05). Urban green space and commercial land area were negatively correlated with circulatory disease mortality, and regression coefficients were −0.550 and −0.280, respectively (P<0.05). On the contrary, the increase of urban road area, residential land ratio, and the degree of land use mix were positively associated with circulatory disease mortality, and their regression coefficients were 0.322, 0.283, and 0.176, respectively (P<0.05). When the level of urban economic development was low, the impact of commercial land use ratio on circulatory diseases was stronger, and the regression coefficient was −0.476 (P<0.05). When urban air pollution worsened, the impacts of per capita green coverage area and per capita urban road area on the disease were more prominent, and the regression coefficients were −0.528 and 0.372, respectively (P<0.05). Conclusion There is a significant correlation between urban built environment and mortality of circulatory diseases. To be specific, circulatory disease mortality has a negative correlation with per capita green coverage area and commercial land use ratio, and a positive correlation with per capita urban road area, residential land ratio and degree of land use mix.

Objective:To evaluate the feasibility of a new ultrasonic parameter to assess right ventricular-pulmonary artery (RV-PA) coupling in patients with acute pulmonary embolism (APE).Methods:A retrospective analysis was performed in 140 patients with APE diagnosed by computed tomography pulmonary angiography (CTPA) in the Second Affiliated Hospital of Harbin Medical University from August 2017 to June 2020. According to the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/PASP) ratio cutoff value 0.40 mm/mmHg reported by the European Society of Cardiology in 2020, the patients were divided into the coupling group ( n=99) and the uncoupling group ( n=41). The conventional ultrasonic parameters of the 2 groups were measured, and then several ultrasonic parameter ratios were obtained. The new ultrasonic parameter, which can replace the TAPSE/PASP ratio, was screened out by Spearman correlation analysis, and ROC curve was plotted to calculate the diagnostic efficacy of this parameter. Results:①Compared with the coupling group, patients in the uncoupling group were older and more likely to be accompanied by dyspnea and venous thrombosis in the lower extremities (all P<0.05), but there was no significant difference in other general data(all P>0.05); ②Compared with the coupling group, tricuspid regurgitation velocity (TRV), tricuspid regurgitation pressure gradient(TRPG), PASP, right ventricle end-diastolic transverse diameter(RVTD), inferior vena cava(IVC) diameter and the ratio of early diastolic tricuspid inflow to tricuspid lateral annular velocity(E/e′), in the uncoupling group increased significantly (all P<0.05), and TAPSE, peak systolic velocity of tricuspid annulus(s′), TAPSE/PASP ratio, TAPSE/TRPG ratio, TAPSE/RVTD ratio and s′/TRPG ratio decreased significantly (all P<0.05); ③The TAPSE/TRPG ratio was highly correlated with TAPSE/PASP ratio ( rs=0.970, P<0.001); The TAPSE/TRPG ratio was still highly correlated with TAPSE/PASP ratio in the uncoupling and coupling groups ( rs=0.966, 0.922; all P<0.001). ④ROC analysis showed that the area under curve for TAPSE/TRPG in diagnosing RV-PA coupling was 0.992. At the cutoff of TAPSE/TRPG <0.625 mm/mmHg for indicating RV-PA coupling, the sensitivity and specificity were 97.6% and 92.9%, respectively. Conclusions:TAPSE/TRPG ratio can be used as a new ultrasonic parameter to reflect RV-PA coupling, which is helpful for clinical identification of APE patients with high risk and poor prognosis.