Effect of co-morbid chronic kidney disease on the accuracy of cardiac troponin levels for diagnosis of acute myocardial infarction / 南方医科大学学报

OBJECTIVE@#To evaluate the accuracy of cardiac troponin (cTn) levels in the diagnosis of acute myocardial infarction (AMI) in patients with chronic kidney disease (CKD) and explore a potential strategy for improving the diagnostic accuracy.@*METHODS@#We retrospectively analyzed the data from patients with high-risk chest pain admitted in Zhujiang Hospital from January, 2018 to December, 2020, including 126 patients with and 272 patients without CKD, and 122 patients diagnosed to have AMI and 276 patients without AMI. The baseline clinical data of the patients and blood test results within 12 h after admission were collected.@*RESULTS@#In patients without AMI, cTnT level was significantly higher in those with co-morbid CKD than in those without CKD (P < 0.001), and showed a moderate negative correlation with eGFR (rs=- 0.501, P < 0.001), while cTnI level did not differ significantly between the two groups (P=0.72). In patients with CKD, the optimal cutoff level was 0.177 μg/L for cTnT and 0.415 ng/mL for cTnI for diagnosis of AMI, for which cTnI had a higher specificity than cTnT. The diagnostic model combining both cTnT and cTnI levels [P=eY/(1+ eY), Y=6.928 (cTnT)-0.5 (cTnI)-1.491] had a higher AUC value than cTn level alone.@*CONCLUSION@#In CKD patients, the cutoff level of cTn is increased for diagnosing AMI, and cTnI has a higher diagnostic specificity than cTnT. The combination of cTnT and cTnI levels may further improve diagnostic efficacy for AMI.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Report on Cardiac Gross Pathologic Measurements of Sudden Cardiac Death in Adults / 法医学杂志

OBJECTIVES@#To analyze the gross pathological data of sudden cardiac death (SCD) with different causes, to provide data support for the identification of sudden cardiac death with unknown causes.@*METHODS@#A total of 167 adult SCD cases in the archive of the Forensic Expertise Institute of Nanjing Medical University from 2010 to 2020 were collected. The gross pathological data of SCD cases were summarized and the characteristics of different causes of death were statistically analyzed.@*RESULTS@#The ratio of male to female SCD cases was 3.4∶1. Coronary heart disease was the leading cause of SCD, and mainly distributed in people over 40 years old. SCD caused by myocarditis was mainly distributed in young people and the mean age of death was (34.00±9.55) years. By analyzing the differences in cardiac pathological parameters of SCD with different causes, it was found that the aortic valve circumference was significantly dilated in the SCD caused by aortic aneurysm or dissection (P<0.05). The heart weight of SCD caused by aortic aneurysm or dissection and combined factors was greater, and both pulmonary and tricuspid valvular rings were dilated in the SCD caused by combined factors in adult males (P<0.05).@*CONCLUSIONS@#Various gross pathological measures of SCD with different causes are different, which has reference value in the cause of death identification of SCD.

A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance / 药物分析学报

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50％of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

Radiation environment monitoring and analysis of exempted X-ray devices / 中国辐射卫生

Objective To propose specific suggestions for exemption management of X-ray devices applying for exemption management. Methods The weight analysis of influence of shielding thickness and tube voltage on the radiation dose leakage of low-energy X-ray devices was carried out through test analysis, and the radiation status of 50 X-ray devices applied for end-user exemption in Shenzhen, China was investigated. Results There was no significant correlation between the ambient dose equivalent rate and the tube voltage and tube current of the X-ray device. The ambient dose equivalent rate of 50 X-ray devices was 0.16-1.20 μSv/h. Among them, 8 X-ray devices had radiation dose leakage, that is, the ambient dose equivalent rate was greater than 0.36 μSv/h; the ambient dose equivalent rate of one X-ray device was 1.2 μSv/h, exceeding exemption management requirements. Conclusion Applications for exemption management and filing of X-ray devices should be treated differently, and their own shielding effect and inherent safety have a greater impact on radiation safety, which should be focused on.

Non-Contrast Cine Cardiac Magnetic Resonance Derived-Radiomics for the Prediction of Left Ventricular Adverse Remodeling in Patients With ST-Segment Elevation Myocardial Infarction

Objective@#To investigate the predictive value of radiomics features based on cardiac magnetic resonance (CMR) cine images for left ventricular adverse remodeling (LVAR) after acute ST-segment elevation myocardial infarction (STEMI). @*Materials and Methods@#We conducted a retrospective, single-center, cohort study involving 244 patients (random-split into 170 and 74 for training and testing, respectively) having an acute STEMI (88.5% males, 57.0 ± 10.3 years of age) who underwent CMR examination at one week and six months after percutaneous coronary intervention. LVAR was defined as a 20% increase in left ventricular end-diastolic volume 6 months after acute STEMI. Radiomics features were extracted from the oneweek CMR cine images using the least absolute shrinkage and selection operator regression (LASSO) analysis. The predictive performance of the selected features was evaluated using receiver operating characteristic curve analysis and the area under the curve (AUC). @*Results@#Nine radiomics features with non-zero coefficients were included in the LASSO regression of the radiomics score (RAD score). Infarct size (odds ratio [OR]: 1.04 (1.00–1.07); P = 0.031) and RAD score (OR: 3.43 (2.34–5.28); P < 0.001) were independent predictors of LVAR. The RAD score predicted LVAR, with an AUC (95% confidence interval [CI]) of 0.82 (0.75–0.89) in the training set and 0.75 (0.62–0.89) in the testing set. Combining the RAD score with infarct size yielded favorable performance in predicting LVAR, with an AUC of 0.84 (0.72–0.95). Moreover, the addition of the RAD score to the left ventricular ejection fraction (LVEF) significantly increased the AUC from 0.68 (0.52–0.84) to 0.82 (0.70–0.93) (P = 0.018), which was also comparable to the prediction provided by the combined microvascular obstruction, infarct size, and LVEF with an AUC of 0.79 (0.65–0.94) (P = 0.727). @*Conclusion@#Radiomics analysis using non-contrast cine CMR can predict LVAR after STEMI independently and incrementally to LVEF and may provide an alternative to traditional CMR parameters.

Study on the fingerprint of total saponins from Mussaenda pubescens and the spectrum-effect relationship of its hepatoprotective activity / 中国药房

OBJECTIVE To establish the fingerprint of total saponins from Mussaenda pubescens， and to study the spectrum- effect relationship of its hepatoprotective activity. METHODS Ten batches of total saponins from M. pubescens from different origins were prepared using 75% ethanol as solvent. High-performance liquid chromatography （HPLC） and the Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition） were used to draw the fingerprints of 10 batches of total saponins from M. pubescens. The similarity evaluation and identification of common peaks were conducted. The same HPLC method was adopted to determine the contents of five triterpenoid saponins （mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G and mussaendoside O）. The hepatoprotective effect of total saponins from M. pubescens was investigated by establishing carbon tetrachloride-induced acute liver injury model mice， and the spectrum-effect relationship was studied by using grey correlation analysis. RESULTS There were 11 common peaks in 10 batches of total saponins from M. pubescens， 5 of which were identified， i.e. mussaendoside H （peak 3）， mussaendoside U （peak 7）， mussaglaoside C （peak 8）， mussaendoside G （peak 9） and mussaendoside O （peak 11）； the similarities of 10 batches of samples ranged 0.940- 0.991. Average contents of mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G， mussaendoside O were 0.01- 0.05， 0.10-0.21， 0.10-0.18， 0.03-0.08， 0.20-0.40 mg/g， respectively. Ten batches of total saponins from M. pubescens could generally reduce the contents of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum， and tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in liver tissue of model mice （P＜0.05 or P＜0.01）. The E-mail：13878195336@139.com correlation between the common peak areas and the contents of ALT， AST， TNF-α， IL-6 and IL-1β were 0.602-0.757， 0.585-0.833， 0.593-0.795， 0.618-0.820， 0.607-0.804， respectively； the peaks with high correlation were peaks 11， 9 and 8 in order. CONCLUSIONS Ten batches of total saponins from M. pubescens have similar components， and the average contents of mussaendoside H， mussaendoside U， mussaglaoside C， mussaendoside G and mussaendoside O are different. The batches of samples have a certain degree of hepatoprotective effect； mussaendoside O， mussaendoside G and mussaglaoside C may be its main active components.

Effect of dexmedetomidine on TXNIP/ASK1 signaling pathway in a mouse model of intestinal ischemia-reperfusion / 中华麻醉学杂志

Objective:To evaluate the effect of dexmedetomidine on the thioredoxin-interacting protein (TXNIP)/apoptosis signal-regulated kinase 1 (ASK1) signaling pathway in a mouse model of intestinal ischemia-reperfusion (I/R).Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), TXNIP inhibitor resveratrol group (Res group) and dexmedetomidine group (Dex group). The mouse model of intestinal I/R injury was developed by clamping the superior mesenteric artery for 45 min followed by 120-min reperfusion in anesthetized animals. Resveratrol 30 mg/kg was intraperitoneally injected before developing the model in Res group, and dexmedetomidine 25 μg/kg was intraperitoneally injected at 30 min before ischemia in Dex group. Blood samples were collected by cardiac puncture at the end of 120-min reperfusion, then the mice were sacrificed, and the small intestine tissues were removed for microscopic examination and for determination of the serum diamine oxidase (DAO) concentration (by enzyme-linked immunosorbent assay) and expression of TXNIP, ASK1 and cleaved-caspase-3 in small intestinal tissues (by Western blot). The apoptosis rate of intestinal epithelial cells was calculated. The intestinal damage was assessed and scored according to Chiu. Results:Compared with group Sham, the Chiu′s score, serum DAO concentrations and apoptosis rate of intestinal epithelial cells were significantly increased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in group Res ( P<0.05). Compared with I/R group, the Chiu′s score, serum DAO concentration and apoptosis rate of intestinal epithelial cells were significantly decreased, and the expression of TXNIP, ASK-1 and cleaved-caspase-3 was down-regulated in Dex group ( P<0.05). Conclusions:The mechanism by which dexmedetomidine alleviates intestinal I/R injury may be related to inhibition of the TXNIP/ASK1 signaling pathway and reduction of cell apoptosis in mice.

Advances in potential drugs for improvement of energy metabolism in heart failure / 药学实践杂志

Heart failure (HF) is a global public health problem with high morbidity and mortality. Numerous studies have shown that HF is caused by severe disturbance of energy metabolism, resulting in insufficient cardiac energy supply. This lack of energy could lead to a failure of the heart to pump blood and a failure of energy metabolism in other organs throughout the body. Currently, therapeutics of HF work by reducing heart rate and cardiac preload and afterload, symptomatic treatment, or delaying the progression of the disease. However, drugs targeting heart energy metabolism have not been developed. the main characteristics of cardiac energy metabolism, metabolic changes during HF were summarized and drugs that improve cardiac function through energy metabolism were discussed, which could provide a new research direction for the development and application of drugs in treatment of heart failure.

Effect of hemopurification on acute chlorfenapyr poisoning / 中华急诊医学杂志

Objective:To evaluate the therapeutic effect of hemopurification on acute chlorfenapyr poisoning according to the blood concentration of chlorfenapyr and to provide experience for clinical treatment.Methods:Two patients who presented to our Emergency Department following an ingestion of chlorfenapyr and then were treated with hemopurification in 2022 were included. The concentrations of chlorfenapyr and its highly toxic metabolite tralopyril were dynamically monitored, and the clinical data of the patients were collected.Results:Case 1 was given hemoperfusion for the first time 13 hours after ingestion. During l hour hemoperfusion, the tralopyril decreased by 28.82%. The concentration increased and exceeded the pre-perfusion level after 2 hours of hemoperfusion. After three times of hemoperfusion, the concentrations of chlorfenapyr and tralopyril were still higher than those before the first time, reaching 248 ng/mL and 1 307 ng/mL respectively. The concentration of chlorfenapyr showed a downward trend after 130 h, and the tralopyril in blood reached the peak 3 164 ng/mL at 130 h and decreased to 2 707 ng/mL at 178 h. In case 2, the blood chlorfenapyr and tralopyril concentration was 392 ng/mL and 7 598 ng/mL respectively 150 hours after ingestion. The blood chlorfenapyr concentration decreased by 37.75% respectively after first hemoperfusion, and the tralopyril concentration decreased by 38.02% respectively. During 85 hours of continuous veno-venous hemodiafiltration (CVVHDF), the concentration of tralopyril was maintained at 4 234~6 410 ng/mL. Case 1 was followed up to 12 days and lost follow-up. Case 2 died and the survival time was 247 hours.Conclusions:Hemoperfusion can scavenge tralopyril, but CVVHDF has poor scavenging ability for tralopyril. And the apparent volume of distribution (Vd) of chlorfenapyr and tralopyril are large. After ingestion, chlorfenapyr spreads to various tissues quickly, and it is easy to accumulate in the adipose tissue. The chlorfenapyr in the tissue slowly is released back to the blood and stays in the blood for a long time. The peak concentration of chlorfenapyr appeared earlier than that of tralopyril. Clinicians should pay attention to the early removal of toxins from the digestive tract.

Analysis of epidemiology and clinical characteristics of patients with poisons purchase online / 中华急诊医学杂志

Objective:To explore the clinical characteristics of poisoned patients with poisons purchase online.Methods:A retrospective case-control study was conducted on poisoned patients purchased poisons online from 1st January 2021 to 31th May 2022 in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University. The clinical data including sex, age, way of medical treatment, cause of poisoning, exposure routes, category of toxic drugs, gastric lavage, toxic detection and prognosis of patients were collected and compared with those patients obtained poisons at stores as the control group.Results:Totally 318 poisoned patients were included in this study, of which 44 (13.8%) were obtained poisons online. Compared with the patients obtained poisons at stores, the patients obtained poisons online were younger ( P<0.001), and had higher proportion of suicide intention ( P=0.006), more oral route exposure ( P=0.029), and more proportions of receiving gastric lavage before transfer to the hospital ( P=0.001). Pesticides and fertilizers with organic heterocycles were the main types of poisons in the online group, and there was no statistical difference in the distribution of poisons compared with the control group. Mixed drug poisoning was the leading cause in both online group (27.8%) and control group (38.8%) in drug overdose poisoned types, followed by dextromethorphan (16.7%) and estazolam (15.5%) in the online group. Conclusions:Young people are the main group getting poisons through the Internet. Health education should be strengthened for this group, and online shopping platforms should pay attention to the poisoning risk of potential overdose drugs or poisons transactions.

Clinical value of sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning / 中华急诊医学杂志

Objective:To explore the clinical value of urine semi-quantitative colorimetry by sodium dithionite reduction method in the diagnosis and treatment of diquat poisoning.Methods:The data of 49 patients with acute diquat poisoning treated in the First Affiliated Hospital of Nanjing Medical University from December 3, 2020 to November 23, 2022 were retrospectively analyzed, the correlation between urine colorimetric results and plasma diquat concentration was observed, and the predictive value of urine colorimetric results for target organ damage and prognosis were evaluated.Results:There was a significant correlation between urine colorimetric results and plasma diquat concentration, the correlation coefficient was r=0.89, P <0.01. The cut-off value of urine colorimetry for the predicting the damage of gastrointestinal tract, liver, kidney, and central nervous system injury were 2.5, 3.5, 3.5, 5.5, respectively; in which the urine colorimetric results showed the highest sensitivity in predicting digestive tract injury [ AUC 0.93 (95% CI:0.89-1.00)]. The cut-off value of urine colorimetry for the prognosis of death was 4.5, the positive predictive value was 64.2%, and the negative predictive value was 95.2%. Conclusions:The urine semi-quantitative method can be used for rapid prediction of the plasma diquat concentration range on admission. The urine colorimetry results can also effectively predict the occurrence of organ injury and clinical outcome related to diquat poisoning, which provides evidence for the clinical diagnosis and therapy.

Application of toxicant and drug detection in 895 patients with clinical poisoning diseases / 中华急诊医学杂志

Objective:To explore the diagnostic value of the toxicant and drug detection in clinical poisoning diseases and analyze the clinical characteristics of patients with positive poison test.Methods:This study was a multicenter retrospective cohort study. Sampling and clinical information data were collected between October 1, 2020 and September 30, 2022 from 41 tertiary hospitals in and around Jiangsu province. The clinical characteristics of patients with positive toxicology tests were analyzed, and the correlation between the drug sampling situation and the test results was analyzed..Results:A total of 895 patients with clinical diagnosis or suspected poisoning were enrolled in this study. Among them, 652 patients had positive results, accounting for 72.85%. Among all positive patients, 506 patients were exposed to a single poison and 147 patients were exposed to multiple poisons. The top three poisons were pesticide herbicides (202 cases, 30.98%), sedative and psychotropic drugs (151 cases, 23.16%), and pesticide insecticides (97 cases, 14.88%). Among 541 patients with clear exposure history, the positive rate was 78.19%, and among 354 patients with unclear exposure history, the positive rate was 64.69%. The top three poisons (drugs) of patients with unclear exposure history were sedative and psychotropic (82, 12.58%), herbicide (26, 3.99%), and rodenticide (22, 3.37%). Patients who admitted to hospital for unexplained consciousness disorder, abnormal blood coagulation function and multiple organ dysfunction were more likely to obtain positive poison test results.Conclusions:There is uncertainty in the exposure history of poisoning diseases, so it is necessary to improve the detection of toxic substances as soon as possible. Toxicant testing should be considered when patients have impaired consciousness, abnormal coagulation function and multiple organ dysfunction.

Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis / 中华内科杂志

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Statistical methods of unmeasured confounder control based on negative control theory / 中华流行病学杂志

Controlling unmeasured confounders in non-randomized controlled studies is challenging. Negative control theory is based on the theoretical concept that the test result of negative controls must be negative. Setting appropriate negative control incorporates the specificity of association into population studies for the identification and control of unmeasured confounders. This paper explains the principles to control unmeasured confounders using negative control theory from a statistical perspective. A detailed introduction of derived methods based on negative control theory is also introduced, including adjusted standardized mortality ratio method, calibrating P-value method, generalized difference-in-difference model and double negative control method. The reasonable application of those derived methods is also comprehensively summarized based on representative case studies. Negative control is an important statistical design to identify, revise and control unmeasured confounders and a valuable method for comparative effectiveness research based on real-world data.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

18F-FDG PET/CT Prognostic Role in Diffuse Large B-cell Lymphoma Following Chemotherapy / 中山大学学报(医学科学版)

ObjectiveTo assess the prognostic value of 18F-FDG PET/CT parameters for predicting therapeutic response in diffuse large B-cell lymphoma （DLBCL）. MethodsWe retrospectively analyzed the clinical data and 18F-FDG PET/CT radiomics features of 81 DLBCL patients enrolled between June 2015 and October 2020. Multivariate logistic regression analysis was used to identify the predictive factors for therapeutic response of DLBCL， based on which a predictive model was developed accordingly. The performance of the model was evaluated by receiver operating characteristic （ROC） curves and calibration plots. ResultsDuring the two years after first chemotherapy， 23 patients （28.3%） developed relapse and 58 patients （71.7%） had progression-free survival （PFS）. The analysis for the predictive capability of the binary logistic regression model incorporating the PET/CT features revealed that the imaging features of 18F-FDG PET/CT after chemotherapy were independent prognostic factors for PFS. Among them， SUVTHR-mean2 was the most important factor for predicting therapeutic response in DLBCL patients after chemotherapy， with a cutoff value of 2.00 （AUC=0.81）. Conclusions18F-FDG PET/CT showed a valuable prognostic performance for PFS in DLBCL patients after chemotherapy， with the imaging feature after chemotherapy SUVTLR-mean2 being the optimal independent predictor. Our predictive model of imaging features might have an important prognostic value in assessing the risk of disease progression， guiding the treatment and follow-up protocol， improving therapeutic efficiency and cutting down the medical cost.

A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring / 中国当代儿科杂志

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.

CiteSpace knowledge map of research hotspots and frontiers of Polygalae Radix / 中国中药杂志

In this study, the Web of Science and China National Knowledge Infrastructure(CNKI) were searched comprehensively for the literature about the research on Polygalae Radix. After manual screening, 1 207 Chinese articles and 263 English articles were included in this study. Excel was used to draw the line chart of the annual number of relevant publications. CiteSpace 6.1.R3 was used for the visual analysis of author cooperation, publishing institutions, keyword co-occurrence, keyword clustering, and bursts in the research on Polygalae Radix. The results showed that the number of articles published in Chinese and English increased linearly, which indicated the rising research popularity of Polygalae Radix. WANG J and LIU X were the authors publishing the most articles in Chinese and English, respectively. Shanxi University of Chinese Medicine and Chinese Academy of Medical Sciences were the research institutions with the largest number of Chinese and English publications in this field, respectively. The institutions publishing the relevant articles in English formed a system with the Chinese Academy of Medical Sciences as the core. According to the keywords, the research hotspots of Polygalae Radix included variety selection and breeding, quality standard, extraction and identification of active chemical components, prescription compatibility, processing, clinical medication rules, and pharmacological mechanism. The research frontiers were the molecular mechanisms of Polygalae Radix and its active components in exerting the protective effect on brain nerve, regulating receptor pathways, alleviating anxiety and Alzheimer's disease, as well as data mining and clinical medication summary. This study has reference significance for the topic selection and frontier identification of the future research on Polygalae Radix.

Structural repurposing of SGLT2 inhibitor empagliflozin for strengthening anti-heart failure activity with lower glycosuria

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC50 > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.