Objective To explore the effects of nicotinamide mononucleotide （NMN） on hypertensive rats. Methods Two rat hypertension models including spontaneously hypertensive rats（SHR）and two-kidney two-clip （2K2C） rats were used to be given single, long-term or lifelong administration of NMN respectively. NMN’s effects were assessed comprehensively by monitoring survival time, blood pressure levels, and the extent of organ damage in hypertensive model rats. Results It was revealed that NMN did not exhibit protective effects in terms of lowering blood pressure levels, reducing organ damage or increasing survival time in hypertensive rats. Conclusion This study suggested that NMN did not demonstrate anti-hypertensive effects in rat hypertension models and could provide valuable insights for future clinical observation on NMN.

Objective To study the effect of MT-1207 on blood glucose,blood lipids and atherosclerosis in mice.Methods The apolipoprotein E knockout(ApoE-/-)mice were fed with normal feed,drug feed containing losartan and drug feed containing MT-1207 at a dosage of 30 mg/kg.The body weight,blood glucose and blood lipids were detected,and the plaque area of atherosclerotic was evaluated.8-week-old male C57 mice were fed a high fat diet and given intragastric administration of MT-1207 and losartan at a dose of 30 mg/kg per day.The body weight,blood glucose and lipids levels were also examined to further evaluate the effects of MT-1207 on blood glucose and lipids levels.Results ApoE-/-mice treated with MT-1207 and losartan gained weight faster.There was no significant improvement in blood glucose and lipid levels,and no significant change in atherosclerotic plaque area.MT-1207 and losartan had no significant improvement effect on blood glucose and blood lipids of C57 mice.Conclusion MT-1207 and losartan couldn't improve the levels of blood glucose,blood lipids and atherosclerosis,and couldn't aggravate atherosclerosis.

The injury of vascular endothelial cell function is the beginning of the pathological process of atherosclerosis. Mitochondrial oxidative stress is closely related to vascular endothelial cell function, which causes the dysfunction of vascular endothelial cell by inducing mitophagy, reducing nitric oxide production, inflammation, cellular metabolic imbalance and apoptosis. Meanwhile, vascular endothelial cell could also maintain their homeostasis by regulating mitochondrial oxidative stress. The molecular signaling pathways of the vascular endothelial cell injury caused by mitochondrial oxidative stress in the pathological process of atherosclerosis were outlined in this review, which provided reference for further research on the molecular mechanism between mitochondrial oxidative stress and endothelial damage.

Objective:To compare the safety and efficacy of 7.5 Fr and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm.Methods:Using a prospective randomized controlled study method, 96 patients with upper urinary tract calculi with maximum diameter<1.5 cm admitted to the Department of Urology, Beijing Friendship Hospital, Capital Medical University from August 2020 to May 2022 were selected as the study subjects. The patients were divided into two groups by random number table method: the experimental group and the control group, with 48 patients in each group. The experimental group patients underwent 7.5 Fr flexible ureteroscopic lithotripsy, while the control group patients underwent 9.5 Fr flexible ureteroscopic lithotripsy. Collect preoperative, intraoperative, and postoperative data from these patients, including success rate of ureteral access sheath insertion, surgical time, lithotripsy time, stone-free rate, ureteral injury status, and complications status. The measurement data were expressed as mean±standard deviation ( ± s), Student- t test was used for comparison between groups; the Chi-square test was used for inter-group comparison of count data, and the Mann-Whitney U test was used for inter-group comparison of rank data. Results:The success rate of primary sheath insertion in the experimental group was 93.8% (45/48), and that in the control group was 79.2% (38/48), the difference between the two groups was statistically significant ( P<0.05). There were no statistically significant difference between the experimental group and the control group in terms of surgical time [(52.0±11.0) min vs (55.1±11.4) min, P>0.05] and lithotripsy time [(26.0±9.3) min vs (23.7±8.7) min, P>0.05]. At four weeks after surgery, the stone-free rate in the experimental group was 93.3% (42/45), while that in the control group was 97.4% (37/38), there was no statistically significant difference between the two groups ( P>0.05). In terms of the degree of ureteral injury, there were 17 patients had grade 0 injury, 27 patients had grade 1 injury, 4 patients had grade 2 injury, and no patient had grade 3 injury in the experimental group; there were 9 patients had grade 0 injury, 23 patients had grade 1 injury, 13 patients had grade 2 injury, and 3 patients had grade 3 injury in the control group; the difference between the two groups was statistically significant ( P<0.05). In terms of complications, there were 22 cases of hematuria, 9 cases of pain, 8 cases of bladder spasm, and 2 cases of mild fever in the experimental group; there were 24 cases of hematuria, 12 cases of pain, 9 cases of bladder spasm, and 1 case of mild fever in the control group; there was no statistically significant difference between the two groups ( P>0.05). Conclusion:The application of 7.5 Fr flexible ureteroscopy and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm can achieve good stone-free rates, but the 7.5 Fr flexible ureteroscopy has a higher success rate of sheath insertion and less damage to the ureter.

Objective:To investigate the value of machine learning methods for predicting in-hospital mortality in trauma patients with acute respiratory distress syndrome (ARDS).Methods:A retrospective non-intervention case-control study was performed. Trauma patients with ARDS met the Berlin definition were extracted from the the Medical Information Mart for Intensive CareⅢ (MIMICⅢ) database. The basic information [including gender, age, body mass index (BMI), pH, oxygenation index, laboratory indexes, length of stay in the intensive care unit (ICU), the proportion of mechanical ventilation (MV) or continuous renal replacement therapy (CRRT), acute physiology scoreⅢ(APSⅢ), sequential organ failure score (SOFA) and simplified acute physiology scoreⅡ(SAPSⅡ)], complications (including hypertension, diabetes, infection, acute hemorrhagic anemia, sepsis, shock, acidosis and pneumonia) and prognosis data of patients were collected. Multivariate Logistic regression analysis was used to screen meaningful variables ( P < 0.05). Logistic regression model, XGBoost model and artificial neural network model were constructed, and the receiver operator characteristic curve (ROC) was performed to evaluate the predictive value of the three models for in-hospital mortality in trauma patients with ARDS. Results:A total of 760 trauma patients with ARDS were enrolled, including 346 mild cases, 301 moderate cases and 113 severe cases; 618 cases survived and 142 cases died in hospital; 736 cases received MV and 65 cases received CRRT. Multivariate Logistic regression analysis screened out significant variables, including age [odds ratio ( OR) = 1.035, 95% confidence interval (95% CI) was 1.020-1.050, P < 0.001], BMI ( OR = 0.949, 95% CI was 0.917-0.983, P = 0.003), blood urea nitrogen (BUN; OR = 1.019, 95% CI was 1.004-1.033, P = 0.010), lactic acid (Lac; OR = 1.213, 95% CI was 1.124-1.309, P < 0.001), red cell volume distribution width (RDW; OR = 1.249, 95% CI was 1.102-1.416, P < 0.001), hematocrit (HCT, OR = 1.057, 95% CI was 1.019-1.097, P = 0.003), hypertension ( OR = 0.614, 95% CI was 0.389-0.968, P = 0.036), infection ( OR = 0.463, 95% CI was 0.289-0.741, P = 0.001), acute renal failure ( OR = 2.021, 95% CI was 1.267-3.224, P = 0.003) and sepsis ( OR = 2.105, 95% CI was 1.265-3.502, P = 0.004). All the above variables were used to construct the model. Logistic regression model, XGBoost model and artificial neural network model predicted in-hospital mortality with area under the curve (AUC) of 0.737 (95% CI was 0.659-0.815), 0.745 (95% CI was 0.672-0.819) and 0.757 (95% CI was 0.680-0.884), respectively. There was no significant difference between any two models (all P > 0.05). Conclusion:Logistic regression model, XGBoost model and artificial neural network model including age, BMI, BUN, Lac, RDW, HCT, hypertension, infection, acute renal failure and sepsis have good predictive value for in-hospital mortality of trauma patients with ARDS.

Objective:To examine the survival rates and clinical characteristics of people with newly discovered non-M 3 acute myeloid leukemia (AML) who carry the ASXL1 gene mutation. Methods:From January 2016 to April 2021, the clinical information of patients with newly diagnosed non-M 3 AML at Shandong University's Qilu Hospital was retrospectively examined, and their clinical characteristics and survival were compared and analyzed. Gene mutation was detected by next-generation sequencing. Results:① The study included 256 AML patients who were initially diagnosed and had complete data, including 47 cases of ASXL1 gene mutation-positive (ASXL1 +) patients and 209 cases of ASXL1 gene mutation-negative (ASXL1 -) patients. All patients were divided into three groups: elderly (≥60 years old, n=92) , middle-aged (45-59 years old, n=92) , and young (≤44 years old, n=72) . ②WBC, and age were higher in patients with ASXL1 mutations compared to ASXL1 - patients, while complete response after the first round of treatment (CR 1) was lower ( P<0.05) . In the elderly group, WBC and the proportion of aberrant cells in nuclear cells in ASXL1 + patients were higher than those in ASXL1 - patients ( P<0.05) . In the young group, the WBC of ASXL1 + patients was higher than that of ASXL1 - patients ( z=-2.314, P=0.021) . ③IDH2 mutation and ASXL1 mutation was related ( P=0.018, r=0.34) . In ASXL1 + patients, the proportion of peripheral blasts in the high VAF group (VAF>40% ) was higher than that in the low VAF group (VAF<20% ) , and the proportion of aberrant nuclear cells was higher in the duplication and replacement mutation patients than in the deletion mutation patients ( P<0.05) . ④The overall survival (OS) and progression-free survival (PFS) of ASXL1 + patients were shorter than those of ASXL1 - patients (median, 10 months vs 20 months, 10 months vs 17 months; P<0.05) . The proportion number of aberrant cells in nuclear cells (≥20% ) , complex karyotypes, and TET2 mutation were all independent risk variables that had an impact on the prognosis of ASXL1 + patients, according to multivariate analysis ( P<0.05) . Conclusion:ASXL1-mutated non-M 3 AML patients have higher WBC in peripheral blood, a higher proportion of aberrant cells in nuclear cells, lower CR 1 rate, and shorter OS and PFS. Additionally, a poor prognosis is linked to higher VAF, duplication, and substitution mutations in the ASXL1 gene, as well as the high proportion of aberrant cells in nuclear cells, complex karyotype, and TET2 mutation.

Primary hyperoxaluria (PH) are important causes of kidney stone and chronic kidney stone disease in children. Recurrent kidney stone disease and nephrocalcinosis should alter the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition of genotype and phenotype of PH resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. This paper review the characteristics of genotype and phenotype, genotype-phenotype correlation, current treatment and future gene therapy of PH.

Objective:To explore the influence of storage and delivery conditions of the peripheral blood samples from patients with chronic myeloid leukemia (CML) on the real-time quantitative PCR (RQ-PCR) detection of the BCR-ABL (P210) transcript levels.Methods:The peripheral blood samples of 84 CML patients were collected. The same sample was divided into different groups according to storage time (0, 6, 12, 24, 48, and 72 h) , temperature (room temperature, 18-24 ℃; low temperature, 2-8 ℃) , and vibration conditions (3, 6, and 12 h) . RQ-PCR was used to detect BCR-ABL (P210) transcript levels of the different groups. This study logarithmically transformed (log 10N) the original data [BCR-ABL copy number, ABL copy number, and BCR-ABL (P210) transcript levels]. Results:①Agarose gel electrophoresis showed significant RNA degradation of samples after storage for 48 and 72 h at room temperature. ②Among the overall samples, the BCR-ABL copy number of the samples stored at room temperature for 48 and 72 h was significantly lower than that of the samples stored at low temperature ( P<0.05) . However, the BCR-ABL (P210) transcript levels had no significant difference between samples stored at low temperature and room temperature. ③No significant changes were noted in the BCR-ABL (P210) transcript levels at different storage times (6, 12, 24, 48, and 72 h) regardless of storage temperature ( P>0.05) compared with that at baseline (0 h, -0.56±1.51) . ④ The BCR-ABL copy number of the overall sample only decreased significantly ( P<0.05) at 48 h (2.93±1.59) and 72 h (2.79±1.42) compared with that at baseline (0 h, 3.35±1.60) when stored at room temperature. The ABL copy number in the overall sample decreased significantly at 48 and 72 h (whether low and room temperature; P<0.05) . However, no significant changes were noted in the BCR-ABL (P210) transcript levels after vibration for 3 h (-1.29±1.81) , 6 h (-1.24±1.72) , and 12 h (-1.18±1.68; P>0.05) compared with that at baseline (0 h, -0.60±1.37) . Conclusion:Sample storage time, storage temperature, and vibration can interfere with the results of BCR-ABL and ABL copy number but have no significant effect on the quantitative determination of BCR-ABL (P210) transcript levels. This study provides strong support for the feasibility of transregional transportation of peripheral blood samples from patients with CML.

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

OBJECTIVE: To investigate the effect of SRC kinase inhibitor PP2 on the invasion and metastasis of lung cancer A549 cells and explore its molecular mechanism. METHODS: MTT assay was used to evaluate the inhibitory effect of PP2 on the proliferation of A549 cells. Cell scratch and Transwell assays were performed to assess the invasion and metastatic capacity of A549 cells after treatment with 1, 2, 4, 8, and 16 μmol/L PP2 for 24 h. Western blotting was used to detect the expressions of connexin43 (Cx43) and MMP-2 in the cells after small interfering RNA (siRNA)-mediated silencing or overexpression of Cx43; the changes in the cell invasion and metastasis in response to PP2 treatment after Cx43 silencing or overexpression were investigated. RESULTS: MTT assay showed that treatment with PP2 at 2, 4, 8, 16, and 32 μmol/L significantly inhibited the proliferation of A549 cells in a concentration-dependent manner. Treatments with PP2 at 1, 2, 4, 8, and 16 μmol/L for 24 h also concentration-dependently lowered the invasion and metastatic abilities of the cells ( < 0.05). At 4 and 8 μmol/L, PP2 significantly increased the expression level of Cx43 protein and decreased the expression level of MMP-2 protein. Overexpression of Cx43 significantly enhanced the inhibitory effect of PP2 on the cell invasion and metastasis, and Cx43 silencing significantly attenuated the inhibitory effect of PP2 ( < 0.05). CONCLUSIONS PP2 treatment can suppress the invasion and metastasis of A549 cells possibly by modulating the expression of Cx43.
A549 Cells ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Connexin 43 ; Humans ; Lung Neoplasms ; Neoplasm Invasiveness ; Protein Kinase Inhibitors ; src-Family Kinases