Objective To investigate the effect of hydromorphone postconditioning on ischemiareperfusion (I/R) injury in isolated rat hearts and the role of mitochondial permeability transition pore (mPTP).Methods Male Sprague-Dawley rats, aged 2-3 months, weighing 250-320 g, were used in the study.The rats were heparinized and anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The hearts were excised, and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 36.5-37.5 ℃.Forty isolated rat hearts were randomly divided into 4 groups (n=10 each)using a random number table: control group (group C), group I/R, hydromorphone postconditioning group (group H), and hydromorphone postconditioning + mPTP opener lonidamine group (group HL).Group C was continuously perfused with K-H solution for 120 min.Group I/R was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group I/R was perfused with K-H solution for another 30 min.Group H was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group H was perfused with K-H solution containing 0.3 μmol/L hydromorphone for 10 min, and then with K-H solution for 50 min.Group HL was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group HL was perfused with K-H solution containing 0.3 μmol/L hydromorphone and 30 μmol/L lonidamine for 10 min, and then with K-H solution for 50 min.At 30 min of equilibration (T0), and 30 and 60 min of reperfusion (T2,3), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP) , ±dp/dtmax, heart rate (HR), and coronary flow (CF) were measured.The concentrations of lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB) , and troponin-T (Tn-T) in the coronary effluent were determined at T0 and T3.The coronary effluent was collected at T0 and 15 min of reperfusion (T1),nicotinamide-adenine dinucleotide (NAD+) concentrations were measured using enzyme-linked immunosorbent assay to reflect the degree of mPTP opening.The myocardial infarct size was determined at T3 by TTC staining.Results Compared with group C, LVDP, HR, ±dp/dtmax and CF were significantly decreased, and LVEDP was increased at T2,3, and the concentrations of LDH, CK-MB and Tn-T in the coronary effluent, myocardial infarct size at T3, and NAD+ concentrations in the coronary effluent at T1 were increased in group I/R (P＜0.05).Compared with I/R and HL groups, LVDP, ±dp/dt CF and HR were significantly increased, and LVEDP was decreased at T2,3, and the concentrations of LDH, CK-MB and Tn-T in the coronary effluent, myocardial infarct size at T3, and NAD+ concentrations in the coronary effluent at T1 were decreased in group H (P＜0.05).Conclusion Hydromorphone postconditioning can reduce myocardial I/R injury in isolated rat hearts, and the mechanism is related to inhibition of mPTP opening.

The stable isotope labeling by amino acids in culture (SILAC) based quantitative proteomics serves as a gold standard because of the high accuracy and throughput for protein identifications and quantification. In this study, we discussed the application of SILAC technology in mammal model, and developed quantitative internal standard for comparative proteomics of disease model. The C57BL/6J mice fed by special diet containing the 13C6-Lysine and bred F2 generation. We identified and analyzed total proteins of 9 mice tissues of F2 generation, including brain, lung, heart, stomach, intestine, liver, spleen, kidney, and muscle. Quantitative analysis information could evaluate the mice and different tissues' labeling efficiency. Liver was the most efficient, brain the least, and the labeling efficiency were 96.34%±0.90% and 92.62%±1.98% respectively. The average of the labeling efficiency of F2 generation was 95.80%±0.64%, which met the international standard (≥ 95%) for SILAC quantitative proteomics effective study. SILAC technology was successfully extended to mammalian model system, which will provide powerful tools for the mechanism study of the pathophysiology process with mouse model.
Amino Acids ; chemistry ; Animals ; Diet ; veterinary ; Isotope Labeling ; Lysine ; chemistry ; Mice ; Mice, Inbred C57BL ; Proteins ; chemistry ; Proteomics ; methods

Objective:To analyze the effect of individualized exercise intervention on weight loss and improvement of metabolic indexes in individuals with metabolic syndrome (MS).Methods:This study was a randomized controlled trial. A total of 1 200 MS patients who underwent health examinations in the Beijing Aerospace General Hospital Healthy Management Center from 2019 to 2022 were selected as the research subjects. The patients were randomly divided into the experimental group (600 cases) and the control group (600 cases) by random number table. Based on the patient′s physical fitness data, a 3-month personalized exercise intervention was implemented for the experimental group, which included aerobic exercise 3 to 4 times/week combined with resistance exercise≥2 times/week, and MS-related health examinations were given too. The control group only received physical examination. Paired t-test was used to compare the changes in weight and metabolic-related indicators before and after the intervention in the two groups. Two-sample t-test was used to compare the differences in intervention effects between groups. The effect of personalized exercise intervention on weight loss and improvement of metabolic indicators in the MS population was analyzed. Results:After the intervention, the weight, body mass index, waist-to-hip ratio, resting heart rate, systolic blood pressure, diastolic blood pressure, fasting glucose, low-density lipoprotein, total cholesterol esters, and triglyceride levels in the experimental group were all significantly lower than those before [(72.5±12.9) vs (74.2±13.6) kg, (27.3±3.5) vs (27.9±3.5) kg/m2, 0.87±0.08 vs 0.91±0.08, (71±7) vs (74±9) times/min, (131±11) vs (138±14) mmHg (1 mmHg=0.133 kPa), (80±8) vs (85±9) mmHg, (6.0±1.1) vs (6.9±1.6) mmol/L, (2.78±0.78) vs (3.12±0.77) mmol/L, (4.62±1.04) vs (5.22±0.97) mmol/L, (1.36±0.42) vs (2.59±2.01) mmol/L], but the high-density lipoprotein level was significantly higher than that before [(1.31±0.31) vs (1.27±0.29) mmol/L] (all P<0.05). The weight, body mass index, waist-to-hip ratio, systolic blood pressure, low-density lipoprotein, total cholesterol esters, and triglyceride levels after the intervention in the control group were all significantly higher than those before [(68.1±5.9) vs (67.1±5.9) kg, (25.3±2.4) vs (24.9±2.4) kg/m2, 0.83±0.07 vs 0.82±0.06, (127±12) vs (125±12) mmHg, (3.50±1.45) vs (3.20±1.21) mmol/L, (5.50±1.80) vs (5.30±1.52) mmol/L, (1.59±0.82) vs (1.40±0.65) mmol/L], but the high-density lipoprotein level was significantly lower than that before the intervention [(1.28±0.28) vs (1.38±0.28) mmol/L] (all P<0.05). The intervention effects on weight, body mass index, waist-to-hip ratio, heart rate, systolic blood pressure, diastolic blood pressure, glucose, high-density lipoprotein, low-density lipoprotein, total cholesterol and triglycerides levels in the experimental group were all significantly better than those in the control group [(-1.4±13.3) vs (1.0±5.9) kg, (-0.6±3.5) vs (0.4±2.4) kg/m2, -0.04±0.08 vs 0.01±0.06, (-3±8) vs (0±7) times/min, (-7±12) vs (2±12) mmHg, (-5±9) vs (0±8) mmHg, (-0.9±1.4) vs (0±0.5) mmol/L, (0.04±0.30) vs (-0.10±0.28) mmol/L, (-0.34±0.77) vs (0.30±1.34) mmol/L, (-0.60±1.00) vs (0.20±1.66) mmol/L, (-1.23±1.45) vs (0.19±0.74) mmol/L ] (all P<0.001). Conclusion:Individualized exercise intervention can effectively promote weight loss and improve metabolic-related indicators in MS patients.

The present paper is to research the expression level of the mRNA of scavenger receptor class B type 1-receptor of high-density lipoprotein in endothelial cells after being treated by different shear stress. The second to fourth generations of the cultured human umbilical vein endothelial cells (HUVECs) were used in the experiment. The cells were divided into two groups. The first group was the control group which was not dealt with shear stress; the second group was the experimental group which concluded low shear stress group (4.2 dyne/cm2), moderate shear stress group (8.4 dyne/cm2) and high shear stress group (15 dyne/cm2). The load time was 1h, 2h, 4h and 8h, respectively. Harvesting the cells and extracting total RNA after being treated by different shear stresses, the expression level of the SR-B1 mRNA was detected by semi-quantitative RT-PCR technic. It was found that the expression of SR-B1 mRNA became weaker and weaker compared to the control group when it was stimulated continuously by the low shear stress, the lowest expression of SR-B1 mRNA appeared at 8h. In the moderate shear stress group, the expression of SR-B1 mRNA increased obviously. Compared to the control group, there was significant difference after being treated with 2h. In the high shear stress group, the expression of SR-B1 mRNA increased immediately when it was stimulated by the shear stress. And the expression of SR-B1 mRNA arrived peak value at 4h. Compared to the control group, there was significant difference after being treated for 1h. It was concluded that the harmful mechanism of the low shear stress is that it can increase the incidence of the atherosclerosis by reducing the reverse cholesterol transport and endothelial protection through decreasing the expression of the SR-B1. Otherwise, the high shear stress prevent the genesis of atherosclerosis by the contrary mechanism.
Atherosclerosis ; etiology ; Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; cytology ; metabolism ; Humans ; RNA, Messenger ; genetics ; metabolism ; Scavenger Receptors, Class B ; genetics ; metabolism ; Stress, Mechanical

Objective:To compare the efficacy of double Z-shaped suture and modified Kessler suture in the repair of acute closed Achilles tendon rupture.Methods:A retrospective cohort study was conducted to analyze the clinical data of 27 patients with acute closed Achilles tendon rupture admitted to the Second Affiliated Hospital of Xi′an Jiaotong University from July 2018 to July 2022, including 24 males and 3 females, aged 14-53 years [(35.7±8.2)years]. All the patients underwent primary open surgical repair of the Achilles tendon, among whom 16 patients were treated with the double Z-shaped suture technique (double Z-shaped suture group) and 11 with the modified Kessler suture technique (modified Kessler suture group). Visual analogue scale (VAS) scores preoperatively and at 2, 4, and 6 weeks postoperatively as well as at the last follow-up were compared between the two groups. American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, Achilles tendon total rupture scores (ATRS), ankle range of motion (dorsiflexion and plantarflexion angles), and shear wave elastography (SWE) [with its results recorded as shear wave velocity (SWV)] were applied to evaluate the recovery of tendon function and quality. High-frequency ultrasonography was also used to evaluate the recovery of morphological structure of the Achilles tendon and soft tissue adhesion. Tolerance to early rehabilitation at 2 weeks postoperatively and the incidence of postoperative complications were compared between the two groups.Results:All the patients were followed up for 6-12 months [(9.6±1.3)months]. There was no statistically significant difference in preoperative VAS scores between the two groups ( P>0.05). At 2, 4, and 6 weeks postoperatively, the VAS scores in the double Z-shaped suture group were 4.6(4.0, 5.0)points, 1.6(1.0, 2.0)points, and 0.5(0.0, 1.0)points respectively, significantly lower than those in the modified Kessler suture group [6.9(6.0, 8.0)points, 2.5(2.0, 3.0)points, and 1.4(1.0, 2.0)points] ( P<0.05 or 0.01). At the last follow-up, the VAS decreased to 0.0(0.0, 0.0)points in both groups. VAS score in the double Z-shaped suture group significantly decreased at 2 weeks postoperatively compared to that preoperatively, with a consistent downward trend observed at all the postoperative time points ( P<0.05). In the modified Kessler suture group, there was no significant difference in VAS scores preoperatively and at 2 weeks postoperatively ( P>0.05), but a downward trend was noted at 4 and 6 weeks postoperatively and at the last follow-up ( P<0.05). There were no significant differences in AOFAS ankle-hindfoot scores, ATRS or SWV at 2, 4, and 6 weeks postoperatively and at the last follow-up ( P>0.05). At 2, 4, and 6 weeks postoperatively, dorsiflexion angles in the double Z-shaped suture group were (-18.2±3.9)°, (-13.7±2.8)°, and (-6.6±2.4)° respectively, significantly better than those in the modified Kessler suture group [(-24.1±2.7)°, (-18.3±3.0)°, and (-12.0±2.8)°] ( P<0.01). No significant difference in dorsiflexion angles was observed between the groups at the last follow-up ( P>0.05). No significant differences in plantarflexion angles were noted at 2 weeks postoperatively and at the last follow-up ( P>0.05). At 4 and 6 weeks postoperatively, plantarflexion angles in the double Z-shaped suture group were (37.5±3.8)° and (42.1±3.3)°respectively, significantly better than those in the modified Kessler suture group [(34.6±2.0)° and (38.0±1.4)°] ( P<0.05 or 0.01). Both groups showed increasing trends in AOFAS ankle-hindfoot scores, dorsiflexion and plantarflexion angles, and SWV at 4 and 6 weeks postoperatively, as well as at the last follow-up ( P<0.05 or 0.01). No significant differences were noted in ATRS at 2 and 4 weeks postoperatively in the double Z-shaped suture group ( P>0.05), but significant improvements were observed at 6 weeks postoperatively and at the last follow-up ( P<0.05 or 0.01). In the modified Kessler suture group, no significant changes in ATRS scores were observed at 2, 4 and 6 weeks postoperatively ( P>0.05), except a significant increase at the last follow-up ( P<0.05). High-frequency ultrasonography at 2, 4, and 6 weeks postoperatively as well as at the last follow-up indicated good morphological recovery of the Achilles tendon in both groups, while soft tissue adhesion was significantly less in the double Z-shaped suture group compared with that of the modified Kessler suture group. Thirteen patients (81.3%) in the double Z-shaped suture group and 3 patients (27.3%) in the modified Kessler suture group were observed to tolerate the early rehabilitation at 2 weeks postoperatively as scheduled in the rehabilitation plan ( P<0.05). There was no statistically significant difference in the incidence of postoperative complications between the groups ( P>0.05). Conclusion:Compared with the modified Kessler suture technique, the double Z-shaped suture technique can reduce postoperative pain at an early stage, enhance the restoration of ankle joint mobility, lower the risk of postoperative soft tissue adhesion, and improve tolerance to rehabilitation in the repair of acute closed Achilles tendon rupture.