Reference materials are one of the major approaches to achieve measurement accuracy and metrological comparability. Different functions of reference materials should also be distinguished when applied to mass spectrometry as an emerging technology in clinical laboratory. Proper reference materials for validation, calibration and quality control of measurement method can ensure the accuracy and comparability of test results. Based on the problems of reference materials in clinical mass spectrometry, the precautions for the use of reference materials are summarized in the aspects of measurement method validation, calibrator usage and quality control.

Objective To discuss a method combining serum‐pharmacology and electrophysiology technology ,and to research the mechanism of dilating porcine coronary artery of sodium tanshinone Ⅱ‐A sulfonate (DS‐201) .Methods To give mice intragastric administration solution and measure DS‐201 concentration in mice serum ,and apply the serum to single channel patch to research its effect on big conductance calcium‐activated potassium channels(BKca ) in porcine coronary artery smooth muscle cells (PCASMCs) . Results The linear range of concentration containing DS‐201 serum was 0 .73 to 1 .91 μg/mL (r=0 .997 7) ,the recycle rate was 99 .85% -101 .47% ,and the concentration was(7 .32 ± 4 .25)μg/mL ;the result indicates that serum containing DS‐201 has activa‐tion effects on BKCa in PCASMCs ,while there was no statistical significance (P>0 .05) .Conclusion The establishment method of the alcohol extraction of Danshen is useful and reliable .The HPLC method of measuring DS‐201 concentration is precise .Choosing higher quality drugs or raising bioavailability can improve combination of the serum pharmacology and electrophysiological tech‐nique .

Objective:To comparatively analyze the efficacy of S-1 plus cisplatin as first-line chemotherapy between advanced AFP posi-tive and AFP negative gastric cancer. Methods:A total of 89 eligible patients with advanced gastric cancer from January 2010 to June 2013 were enrolled in this retrospective study. The cases were divided into AFP positive group (n=18) and AFP negative group (n=71) based on serum AFP level before treatment. Both groups received S-1 plus cisplatin as first-line treatment. Results:Significant differ-ences were observed in remission rate (66.7% versus 32.4%, P=0.028) and radical surgical resection rate (44.5% versus 18.3%, P=0.029) after chemotherapy between AFP positive group and AFP negative group. In the two groups, neither progression-free survival nor overall survival (OS) showed any significance (P>0.05) in patients without surgery after chemotherapy. However, the disease-free survival of the two groups with radical surgical resection after chemotherapy was significantly different (median:27.0 months versus 15.6 months, P=0.034). The OS of the AFP positive group was evidently longer than that of the AFP negative group (median:16.0 months versus 11.0 months, P=0.005). Conclusion:As first-line chemotherapy, S-1 plus cisplatin was more effective for the advanced AFP positive gastric cancer and prolonged overall survival.

Objective:To observe the incidence of syncope in patients with acute and critical cardiovascular diseases and to explore the risk factors of death.Methods:925 cases of acute heart failure, acute myocardial infarction, pulmonary embolism, arrhythmia and aortic dissection rupture who participated in Prospective, Multi-CenterRegistered Research Project for Chinese Syncope Patients from March 2018 to March 2020, admitted to the department of emergency of Nanyang Second General Hospital were selected as the research objects. The incidence and mortality of syncope were recorded, and the patients were divided into syncope group and non-syncope group according to whether they were accompanied by syncope or not. The incidence of syncope in male and female patients with different cardiovascular critical diseases, the age and mortality of cardiovascular critical patients with syncope or not were analyzed and compared. Multivariate Logistic regression analysis was used to analyze the risk factors of death, and receiver operating characteristic curve (ROC curve) was drawn to evaluate the predictive value of risk factors on the prognosis of patients.Results:The incidence of syncope in 5 kinds of cardiovascular critical patients from high to low was: acute myocardial infarction 3.03% (28/925), arrhythmia 2.70% (25/925), pulmonary embolism 1.51% (14/925), aortic dissection rupture 1.41% (13/925), acute heart failure 0.65% (6/925), with statistically significant differences ( χ2 = 10.765, P = 0.010). There was no significant difference in the incidence of syncope between male and female patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia and acute heart failure. The age of patients with aortic dissection rupture, acute myocardial infarction and arrhythmia in syncope group were significantly higher than those in non-syncope group [aortic dissection rupture (years old): 66.29±15.64 vs. 57.63±14.23, acute myocardial infarction (years old): 69.55±15.13 vs. 62.10±15.75, arrhythmia (years old): 70.48±14.93 vs. 60.29±16.31, all P < 0.05]. The mortality of patients with pulmonary embolism, aortic dissection rupture, acute myocardial infarction, arrhythmia, acute heart failure in syncope group were significantly higher than those in non-syncope group [pulmonary embolism: 5.81% (5/86) vs. 0.95% (8/839), aortic dissection rupture: 4.65% (4/86) vs. 0.60% (5/839), acute myocardial infarction: 4.65% (4/86) vs. 1.19% (10/839), arrhythmia: 2.33% (2/86) vs. 0.95% (8/839), acute heart failure: 2.33% (2/86) vs. 0.60% (5/839), all P < 0.05]. Multivariate Logistic regression analysis showed that age [odds ratio ( OR) = 2.158, 95% confidence interval (95% CI) was 0.921-4.785, P = 0.000], pulmonary embolism ( OR = 15.391, 95% CI was 8.904-27.314, P = 0.001), aortic dissection rupture ( OR = 13.079, 95% CI was 6.237-25.509, P = 0.000), acute myocardial infarction ( OR = 18.826, 95% CI was 10.420-32.921, P = 0.000), syncope ( OR = 4.940, 95% CI was 1.764-9.287, P = 0.000) were risk factors for the prognosis of patients with acute and critical cardiovascular diseases. ROC curve analysis showed that syncope had a certain predictive value for 28-day prognosis of patients [the area under the ROC curve (AUC) = 0.760, P = 0.000], when the cut-off value was 4.12, the sensitivity was 88.51%, the specificity was 78.05%, the positive predictive value was 81.31%, and the negative predictive value was 84.27%. Conclusions:Syncope is an independent risk factor of death in patients with acute and critical cardiovascular diseases. For patients with syncope as the chief complaint, we should quickly identify the types of acute and critical diseases and assess the risk of sudden death.

Objective:To evaluate the effectiveness of syncope unit in improving the diagnosis efficiency and treatment prognosis of patients with suspected syncope.Methods:The standardized syncope unit was established in the Affiliated Nanyang Second General Hospital of Xinxiang Medical College in 2018. Patients with suspected syncope attending from November 2018 to April 2019 (before the establishment of syncope unit) and from May to October 2019 (after the establishment of syncope unit) were enrolled in the study. There were 109 cases attending before the establishment of syncope unit (control group) and 126 cases attending after establishment (syncope unit group). The positive rate of examination, the treatment and its cost before and after the establishment of syncope unit were compared. After one year, the follow-up rate, recurrence rate, rehospitalization rate, treatment satisfaction and quality of life of patients were documented and compared between two periods.Results:The positive rates of tilt table test [61.90%), Holter monitoring [64.29%(81/126)], exercise stress test [7.14%(9/126)] invasive electrophysiology [40.48%(51/126)], cardiac imaging [9.52%(12/126)] and 24-h blood pressure monitoring [55.56%(70/126)] in syncope unit group were significantly higher than those in control group [44.95%(49/109), 36.70%(40/109), 5.50%(6/109), 10.09%(11/109), 2.75%(3/109) and 40.37%(44/109); χ2=19.28, 23.11, 6.93, 28.18, 15.85 and 11.61,respectively; all P<0.01]. The diagnostic rate of etiology in syncope unit group was significantly higher than that in control group [87.30%(110/126) vs. 77.06%(84/109), χ2=21.70, P<0.01].The time from onset to cardiac assessment and hospitalization time in syncope unit group were significantly shorter than those in control group[(3.68±1.93)h vs. (7.31±2.64)h;(6.17±1.52)d vs. (10.83±2.09)d]. The hospitalization rate [3.17%(4/126) vs. 8.26%(8/109)], hospital mortality [0.79%(1/126) vs. 2.75%(3/109)] and treatment cost [(4.91±1.14) thousands Yuan vs. (7.05±2.53) thousands Yuan] in syncope unit group were significantly lower than those in control group ( t=14.49, P<0.01; t=8.62, P=0.02;χ2=15.83, P<0.01;χ2=10.03, P=0.01; t=6.17, P=0.03).The outpatient follow-up rate [82.54%(104/126)] and treatment satisfaction rate [91.35%(95/104)] in syncope unit group were significantly higher than those in control group [61.47%(67/109) and 64.18%(43/67)]; and the recurrence rate [14.42%(15/104)] and rehospitalization rate [7.69%(8/104)] in syncope unit group were significantly lower than those in control group [40.30%(27/67) and 23.88%(16/67)](χ2=17.30, 20.37, 18.56, 15.08,all P<0.01). The scores of psychological status, physiological status, environmental status, social relations and overall quality of life in contral group were significantly lower than those in syncope unit group (43.62±12.84 vs. 59.13±13.95,43.10±11.31 vs. 5.86±12.09,52.35±12.76 vs. 63.58±13.05,54.87±12.08 vs. 67.91±14.23,58.42±11.87 vs. 69.28±13.51; t=7.74, P=0.03; t=7.50, P=0.03; t=8.66, P=0.02; t=9.77, P=0.01; t=8.46, P=0.02, respectively). Conclusion:The establishment of standardized syncope unit is helpful to improve the diagnosis efficiency and the prognosis of patients with suspected syncope, and also reduce the cost of diagnosis and treatment.

Objective To investigate the correlation between long non-coding RNA (lncRNA)-LOC391533 and inadequate placental spiral artery remodeling in severe preeclampsia (sPE).Methods Thirty-six gravidas who were admitted to the Third Affiliated Hospital of Zhengzhou University with sPE from January 2016 to December 2016 were enrolled in sPE group.An equal number of healthy gravidas who experienced uneventful pregnancy and were of similar age (difference less than two years) and gestational age (difference less than one week) to those in the sPE group served as controls.Scanning electron microscopy was used to measure the luminal area and vessel wall thickness of placental spiral arteries for all gravidas.Levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sVEGFR-1) in placenta tissues and maternal serum samples were detected by Western blot and ELISA.Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of LOC391533 at mRNA level in placenta tissues of the two groups.Independent two samples t-test,Mann-Whitney U test and Spearman correlation analysis were used for statistical analysis.Results (1) The average luminal area of spiral arteries of the sPE group was smaller than that of the control group [(130.1 22.3) vs (188.1 ±21.5) μ m2,t=10.888,P＜0.05],but the average thickness of spiral artery wall was thicker [(122.619.5) vs (98.9±2.5) μ m,t=-8.812,P＜0.05].(2) Compared with the control group,the sPE group showed increased sVEGFR-1 at protein level in both placenta tissues and serum samples [placenta:0.2±0.0 vs 0.4±0.1,serum:(15.6±2.4) vs (50.8±6.1) ng/L,t=-17.569 and-30.699,both P＜0.05],decreased VEGF at protein level in both placenta tissues and serum samples [placenta:0.6 ± 0.1 vs 0.2±0.0,serum:(40.8±3.2) vs (28.1 ±3.2) ng/L,t=18.013 and 16.200,both P＜0.05],and enhanced expression of LOC391533 at mRNA level in placenta tissues (1.00.2 vs 2.40.5,t=-14.799,P＜0.05).(3) Expression of LOC391533 at mRNA level in placenta tissues of the sPE group was positively correlated with spiral artery wall thickness and levels of sVEGFR-1 protein in placenta tissues and serum (r=0.683,0.759 and 0.857,all P＜0.05),and negatively correlated with luminal area and levels of VEGF protein in placenta tissues and serum (r=-0.702,-0.806 and-0.796,all P＜0.05).Conclusions Abnormal expression of VEGF and sVEGF-1 in placenta and serum of patients with sPE may be related to inadequate placental spiral artery remodeling.

Vitamins are classified as either fat-soluble (vitamins A, D, E, K) or water-soluble (vitamins B and vitamin C). Traditional methods of immunoassay have only been developed for vitamins D,B6, B9 and B12. However, they cannot distinguish between vitamin subtypes such as D2, D3 and associated epi isomers (which has higher leveks in infants),giving false positive or negative results. Mass spectrometry has become a gold standard method for small molecule analysis in biological samples with its advantages in speed,resolution,sensitivity and specificity. It is widely used in clinical research and diagnosis and provides an efficient method for simultaneous detection of multivitamins in one injection using one low volume sample collection.

Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

Objective:To explore the feasibility of applying quantitative flow ratio(QFR) to assess the degree of coronary artery functional stenosis before surgery, and to guide coronary artery bypass grafting(CABG) revascularization strategy.Methods:The study prospectively included a total of 154 patients who were electively treated with CABG in the 11th ward of the Department of Cardiac Surgery of Beijing Anzhen Hospital from January 2019 to September 2020, and their coronary angiography visually showed stenosis of the coronary artery to perform QFR analysis to know the diseased blood vessels. For functional stenosis, the surgeon was blinded to the results of QFR analysis before surgery. Collect its baseline data, perioperative data and recent clinical outcomes for summary analysis.Results:One year later, the coronary artery CTA showed that the occlusion rate of functionally significant disease(QFR<0.8) was 5.5%, and that of non-functionally significant disease(QFR≥0.8) was 15.6%. There was no difference in angina class or repeat interventions between patients with or without occluded bypass grafts.Conclusion:According to QFR analysis, coronary arteries with functional non-significant disease have a higher risk of grafts failure than those with functionally significant disease. For coronary arteries with negative QFR lesions, the risk of occlusion of arterial grafts is higher than that of venous. However, this finding is not significantly related to clinical prognosis, because patients with patency or occlusion of the grafts in non-significant lesions have not found excessive angina pectoris or repeated coronary interventions. QFR-guided selection of coronary surgery strategies is safe and feasible.

Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC₅₀ values and achieved picomolar DC₅₀ values and >99% of maximum degradation (D_max) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-MET^Y1230H and c-MET^D1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.