AIM:To study the effects of sesamin (Ses) on attenuating renal injury in spontaneously hyperten-sive rats (SHR) and its relationship with PI3K/AKT/mTOR signaling pathway.METHODS:Spontaneously hypertensive rats were randomly divided into 4 groups:model (SHR) group, Ses low-dose (80 mg/kg) group, Ses high-dose (160 mg/kg) group and captopril (30 mg/kg) group.Another 7 WKY rats were given 0.5%sodium carboxymethylcellulose ( CMC-Na, the solvent was used to dissolve the drugs) as control group.Meanwhile, the rats in drug treatment groups were given the corresponding drugs.All animals were administered intragastrically once a day, and the blood pressure was measured every 2 weeks before and after the beginning of the administration.After 12 weeks, blood urea nitrogen ( BUN) , serum creatinine ( SCr ) , urine micro-albumin ( U-mAlb ) , malondialdehyde ( MDA ) and superoxide dismutase ( SOD ) were measured.The pathological changes of the renal tissues were observed under microscope with HE and Masson staining.Ap-optotic rate of nephridial tissue was determined by TUNEL method.The protein levels of p-AKT, p-mTOR, 4EBP1, S6K1, Bcl-2 and Bax were detected by Western blot.RESULTS:Ses decreased the diastolic blood pressure of SHR, significantly ameliorated the pathological damage in the nephridial tissues.Compared with model group, Ses was obviously reduced the contents of SCr, BUN, U-mAlb, MDA and apoptotic rate of the kidney, decreased the protein levels of p-AKT, p-mTOR, 4EBP1, S6K1 and Bax, and increased the protein expression of Bcl-2 and SOD activity.CONCLUSION:The protective effects of Ses against renal injury in SHR may be related to decreasing blood pressure, increasing anti-oxidative stress, re-straining apoptosis and inhibiting over-activated PI3K/AKT/mTOR signaling pathway.

AIM: To explore the association of single nucleotide polymorphisms of promoter G~ -597 -A, G~ -572 -C, G~ -174 -C and T~ 15 -A, C~ 132 -T in exon 5 of interleukin 6 and lumbar intervebral disc disease. METHODS: The single nucleotide polymorphisms of interleukin 6 gene, including polymorphisms of G~ -597 -A, G~ -572 -C in promoter, G~ -174 -C and T~ 15 -A, C~ 132 -T in exon 5 were analyzed by the polymerase chain reaction and sequencing methods in 81 cases with lumbar intervebral disc disease and 101 healthy controls. The association of single nucleotide polymorphisms of interleukin 6 gene with lumbar intervebral disc disease in two groups was measured. The association of single nucleotide polymorphisms of interleukin 6 gene with lumbar intervebral disc degeneration in those younger than 45-year-old were also measured. RESULTS: The G~ -572 -C polymorphism of interleukin 6 gene was observed, but no single nucleotide polymorphism of G~ -597 -A, G~ -174 -C in promoter and T~ 15 -A, C~ 132 -T in exon 5 in two groups was detected. There was no difference between the distribution of the G~ -572 -C polymorphism of interleukin 6 gene in two groups. In those younger than 45-year-old the association of the single nucleotide polymorphism of interlukin-6 gene and lumbar intervebral disc degeneration was not significant. CONCLUSION: There is G~ -572 -C polymorphism in Chinese. No relation between G~ -572 -C polymorphism of interleukin 6 with lumbar intervebral disc disease and lumbar intervebral disc degeneration was observed.

Aims Toevaluatethepharmacodynamic efficacy of different types of antiangiogenic agents as HM-3 on a non-small cell lung cancer xenografts tumor model .To explore the interaction between the antian-giogenic agents and the tumor microenvironment,and to offer suggestions for clinical therapy.Methods Thenon-smallcelllungcarcinomaxenograftmodelwas established in Balb/c nude mice.The model mice were treated with Docetaxel(10 mg·kg-1 )as the positive control.The mice were parallelly treated with,HM-3 at the doses of 3 mg · kg-1 and 48 mg · kg-1 and, Avastin(5 mg·kg-1 ).The parameters include tumor volume,tumor weight and immunohistochemical analy-sis.Result Animalexperimentsshowedthatdocetaxel had good anti-tumor activity.Tumor growth inhibition by tumor weight of G2 docetaxel(10 mg·kg-1 )group was 60. 80%.Tumor growth inhibition by tumor weight of G3 HM-3(3 mg·kg-1 )group,G4 HM-3(48 mg· kg-1 )group ,G4 Avastin(5 mg·kg-1 )group,were 43. 60%,-34. 80%,44. 40%,respectively.Con-clusion Theantigiogeniceffectisaffectedbytumor growth stage,tumor microenvironment and their work-ing mechanisms.Angiogenesis inhibitors HM-3 has a certain effect of inhibiting tumor growth,but to little a-vail.HM-3 shows on inhibitory effect in a dose-de-pendent manner at the doses of 0~6 mg·kg-1 .HM-3 at a high dose of 48 mg · kg-1 has no inhibitory but promoting effects on human non-small cell lung carci-noma A549 xenografts in nude mice .Special dose-effect relationship indicates that dosage should be paid attention to in the clinical use of blood vessel inhibi-tors.

An innovative approach to quantitatively analyze the histamine and its precursor histidine simultaneously in biological matrices was established for the first time based on double adsorption combined with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).The internal standard was 2-dihydroxybenzoic acid (DHB).The plasma and brain tissue homogenate was protein precipitated with 3-fold acetonitrile, and the supernatant was then sampled for injection analysis.The chromatographic separation of the target components was achieved on an amino chromatography column (ODS-SPXBridge? Amide).Gradient elution was carried out with the mobile phase consisting of solvent A (0.1% formic acid and 1mmol/L ammonium formate in water) and solvent B (acetonitrile).Mass spectrometry was employed for quantitative analysis with ESI ion source in multiple reaction monitoring (MRM) mode.In order to improve the specificity and accuracy, activated carbon and calcite were used for the double adsorption of biological matrices for the first time.The adsorbed matrix was then used for methodology validation.The results showed that histamine and histidine were linear in the quantitative range (correlation coefficient r ≥ 0.999).Accuracy, precision, extraction recovery, matrix effect and stability all met the requirements of biological sample analysis.All results suggested that the present method could not only be efficiently and reliably used for simultaneous quantitative analysis of histamine and histidine in biological samples, but also provide reference for the detection of other endogenous substances.

Ischemia-reperfusion injury (IRI) is a pathophysiological process, which widely exists in organ transplantation and surgery. IRI is mainly manifested with hypoxia injury of organs or tissues during the ischemia period, which could be further aggravated after reperfusion. Ischemia-reperfusion induces tissue cell injury, releases damage-associated molecular pattern and further activates multiple immune cells via pattern recognition receptor, leading to aseptic inflammation and aggravating tissue injury. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), as a critical member of pattern recognition receptor, could activate the stimulator of interferon genes (STING) signal pathway and play an important regulatory role in innate immune response. At present, increasing evidences have shown that cGAS-STING signal pathway plays a significant role in organ IRI. In this article, STING signaling pathway, its role and mechanism in IRI of different organs were reviewed, aiming to provide novel ideas for clinical interventions.

Objective To observe the effect of mild hypothermia on myocardial β-adrenergic receptor (β-AR) signal pathway after cardiopulmonary resuscitation (CPR) in pigs with cardiac arrest (CA) and explore the mechanism of myocardial protection. Methods Healthy male Landraces were collected for reproducing the CA-CPR model (after 8-minute untreated ventricular fibrillation, CPR was implemented). The animals were divided into two groups according to random number table (n = 8). In the mild hypothermia group, the blood temperature of the animals was induced to 33 ℃ and maintained for 6 hours within 20 minutes after return of spontaneous circulation (ROSC) by using a hypothermia therapeutic apparatus. In the control group, the body temperature of the animals was maintained at (38.0±0.5)℃ with cold and warm blankets. The heart rate (HR), mean arterial pressure (MAP), the maximum rate of increase or decrease in left rentricular pressure (+dp/dt max)were measured during the course of the experiment. The cardiac output (CO) was measured by heat dilution methods before CA (baseline), and 0.5, 1, 3, 6 hours after ROSC respectively, the venous blood was collected to detect the concentration of cTnI. Left ventricular ejection fraction (LVEF) was measured with cardiac ultrasound before CA and 6 hours after ROSC. Animals were sacrificed at 6 hours after ROSC and the myocardial tissue was harvested quickly, the mRNA expression of β1-AR in myocardium was detected by reverse transcription-polymerase chain reaction (RT-PCR), the contents of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) were detected by enzyme linked immunosorbent assay (ELISA), the protein content of G protein-coupled receptor kinase 2 (GRK2) was detected by Western Blot. Results After successful resuscitation, the HR of both groups were significantly higher than the baseline values, CO, ±dp/dt max were significantly decreased, MAP were not significantly changed, serum cTnI levels were significantly increased. Compared with the control group, HR at 0.5, 1, 3 hours after ROSC were significantly decreased in mild hypothermia group (bpm: 142.80±12.83 vs. 176.88±15.14, 115.80±11.48 vs. 147.88±18.53, 112.60±7.40 vs. 138.50±12.02, all 1 < 0.01), CO was significantly increased at 1 hours and 3 hours after ROSC (L/min: 3.97±0.40 vs. 3.02±0.32, 4.00±0.11 vs. 3.11±0.59, both 1 < 0.01), +dp/dt max at 3 hours and 6 hours was also significantly increased after ROSC [+dp/dt max (mmHg/s): 3 402.5±612.7 vs. 2 130.0±450.6, 3 857.5±510.4 vs. 2 562.5±633.9; -dp/dt max (mmHg/s): 2 935.0±753.2 vs. 1 732.5±513.6, 3 520.0±563.6 vs. 2 510.0±554.3, all 1 < 0.05], the cTnI was significantly decreased at 3 hours and 6 hours afher ROSC (μg/L: 1.39±0.40 vs. 3.24±0.78, 1.46±0.35 vs. 3.78±0.93, both 1 < 0.01). The left at 6 hours after ROSC in both groups was decreased as compared with that before CA. The LVEF in the mild hypothermia group was higher than that in the control group (0.52±0.04 vs. 0.40±0.05, 1 < 0.05). The mRNA expression of β1-AR, and concentrations of AC and cAMP in hypothermia group were significantly higher than those in control group [β1-AR mRNA (2-ΔΔCT): 1.18±0.39 vs. 0.55±0.17, AC (ng/L):197.0±10.5 vs. 162.0±6.3, cAMP (nmol/L): 1 310.58±48.82 vs. 891.25±64.95, all 1 < 0.05], GRK2 was lower than that in the control group (GRK2/GAPDH: 0.45±0.05 vs. 0.80±0.08, 1 < 0.05). Conclusion Mild hypothermia can reduce the degree of cardiac function injury after CPR, and its mechanism may be related to the reduction of impaired myocardial β-AR signaling after CPR.

BACKGROUND:With the increasing number of tendon transplantation surgeries for tendon injuries,the demand for tendon tissue engineering scaffolds is increasing.Research has found that good pore size and porosity of implants contribute to tissue healing. OBJECTIVE:To review the types of materials currently published for tendon tissue engineering scaffolds and investigate the correlation between various tendon tissue engineering scaffold materials and pores. METHODS:Articles were retrieved on PubMed,Embase,and Web of Science databases,using keywords"tendon"or"ligament"and"tissue scaffold"as well as"porosity"or"permeability".A total of 84 articles meeting the criteria were included to summarize,discuss and anticipate future development directions. RESULTS AND CONCLUSION:The materials used in the research of tendon tissue engineering are mainly divided into two categories:natural tendon scaffold materials and artificial synthetic tendon scaffold materials.Natural scaffold materials include autologous tendons,allogeneic tendons,and xenogeneic tendons.Autogenous tendons and allogeneic tendons have been used in clinical practice for many years.During the preparation of allogeneic tendons and animal experiments,it was found that the process of acellular disinfection resulted in an increase in the pore size and porosity of both types of tendons,but the specific reasons and mechanisms have not been further studied.There are many types of artificial tendon scaffold materials currently being studied,among which artificial ligament products such as Leeds Keio and LARS(Ligament Advanced Reinforcement System)are still in use in some countries.Other materials have not been promoted in clinical practice due to immature technology and other issues.The pores and porosity of artificial tendon scaffold materials also show different trends due to their different materials and preparation techniques.

Objective To investigate the expression of interleukin-3 receptor alpha(CD123)on bone marrow cells in acute myelocytic leukemia(AML)and its clinical significances.Methods By means of Fluorescence-activated cell sorer(FACS)and semi-quantity reverse transcripition polymerase chain reaction(RT-PCR),the expression of IL-3R?(CD123+)protein on CD34+CD38-cells and mRNA in BMMNCs of 62 AML patients of Tianjin Medical University General Hospital from March 2008 to January 2009 and 12 normal controls were detected respectively;Then the correlation between IL-3R? and the clinical stages of AML were analyzed.Results CD34+CD38-CD123+/CD34+CD38-and IL-3R? mRNA in BMMNC of 33 deno-vo or relapsed AML patients were higher than those of control group(P

The aim of the study was to develop a simple, rapid and accurate LC-MS/MS method for the determination of digoxin.Digoxin-d3 was taken as the internal standard (IS), and sample preparation was achieved by liquid-liquid extraction.Chromatographic separation was performed on a Kinetex C18 column (2.1 mm × 50 mm, 2.6 μm; Phenomenex) using an isocratic elution with merely 2 min for each sample.The mobile phase consisted of water and acetonitrile solutions, both containing 1 mmol/L ammonium acetate and 1 mmol/L formic acid (55∶45).The detection was conducted on a TripleQuadTM 4500MD mass spectrometer coupled with electrospray ionization interface under positive-ion multiple reaction monitoring mode.The transitions were m/z 798.5 → 651.3 and m/z 801.6 → 654.4 for digoxin and digoxin-d3, respectively.Results showed that the method was linear over the range of 0.100-20.0 ng/mL.The selectivity, accuracy and precision, recovery and stability of the method were all within the acceptable limits with no matrix effect.This method was successfully applied to a girl treated with digoxin with substantial improvement of therapeutic effect and elimination of toxic reaction, so it can provide valuable fuidance and reference for individualized medication in clinical practice.

Objective:To observe the epidemiological characteristics of spinal metastases by retrospectively analyzing the medical records of multicenter spinal metastases in China.Methods:Patients with spinal metastases were identified from several clinical centers between January 2007 and July 2019. A total of 1 976 patients were included in this study, including 1 129 males (57.14%) and 847 females (42.86%). The mean age was 58.6±11.6 years (range 13-92 years). The demographic characteristics, primary tumor types, spinal involvement of each patient were summarized and their clinical indicators were obtained by consulting medical records, including: Frankel grade, visual analog scale (VAS), metastatic spinal cord compression (MSCC), Tokuhashi revised score, the spinal instability neoplastic score (SINS), Karnofsky performance status (KPS), and history of malignant tumors. Finally, the intervention influencing factors of patients undergoing surgical treatment were statistically analyzed.Results:The ratio of male to female in 1 976 spinal metastases was 1.33∶1. The median age was 59.0, and most patients (63.71%) were in the ages range of 50-69. The average age of female was younger than male, and the difference was statistically significant. The proportion of male patients over 60 years old was higher than females, and the difference was statistically significant. The most common primary tumor was lung cancer (n=730, 36.94%), followed by unknown origin (n=326, 16.50%), breast cancer (n=159, 8.05%), kidney cancer (n=120, 6.07%), gastrointestinal cancer (n=109, 5.52%), etc. The most common primary tumor was lung cancer in both males and females, followed by unknown origin in males and breast cancer in females. In the past 10 years, the proportion of unknown origin has decreased, and the proportion of breast cancer has increased. According to the Tomita score, 1 284 patients (64.98%) were rapid growth tumors, 211 patients (10.68%) were moderate growth tumors, and 481 patients (24.34%) were slow growth tumors. There were 730 patients (57.14%) in the subgroup of the number<3, the most level of which was lumbar vertebrae, with 368 patients (32.60%). The remaining 847 patients (42.86%) were included in the subgroup of the number≥3, the most level of which was multiple-level of spine, with 617 patients (72.85%). Among the 1 976 patients, spinal cord injury occurred in 50.76% of patients, in which 77.18% of patients developed moderate and above pain, 14.02% of patients appeared metastatic spinal cord compression, and only 28.95% of patients had a clear history of primary tumor. In terms of treatment, 34.92% of patients underwent surgery, 5.97% underwent radiotherapy on spinal metastases, 6.02% underwent chemotherapy, and 1.77% underwent targeted therapy. Preoperative Frankel grade, SINS, and Tokuhashi revised score were important factors affecting the surgical treatment of patients.Conclusion:This study describes the epidemiological characteristics of multicenter spinal metastases in detail, which could assist orthopedic surgeons to understand the clinical characteristics of spinal metastases and was of great significance on guiding the clinical diagnoses and scientific researches.