Metabolomics profiling of doxorubicin-induced cardiotoxicity in mice with lung injury / 中国药科大学学报

@#Cardiotoxicity of cancer chemotherapeutics has received considerable attention in recent years.However, the effects of chemotherapy on cardiometabolic perturbation with lung injury have rarely been reported. Thus, we constructed a mouse model of myocardial injury superimposed on lung injury with a combination of bleomycin (BLM) and doxorubicin (DOX).C57BL/6J mice were randomly divided into four groups: control group (CON), BLM group (intratracheal infusion with single doses of 5 mg/kg), DOX group (intraperitoneal injection of 7.5 mg/kg/week, two weeks) and DOX+BLM group. The cardiac injury of mice was evaluated by serum biochemical parameters and histopathology.Cardiometabolic perturbation was investigated using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS).The results showed that, compared with the CON group, BLM alone caused lung injury yet with no significant effects on the cardiometabolic profile; DOX alone had significant perturbations in the cardiometabolic profile, and the main differential metabolites were amino acids, fatty acids, phospholipids, etc.; the combination of BLM and DOX caused more severe disturbance of cardiometabolic homeostasis in mice, especially accumulation of branched-chain amino acids.This study confirmed that DOX can lead to more significant changes in the cardiometabolic profile in the presence of lung injury, with an initial focus on the branched-chain amino acid metabolic pathway.This research provides scientific data for in-depth study of the cardiotoxicity mechanism of chemotherapeutic agents.

Exploration of mini-intelligent PIVAS module construction based on data middle platform service exchange system / 中国药房

The traditional intravenous infusion configuration in medical institutions has the shortcomings of long time and low efficiency， and it is difficult to ensure that the dispensed liquid medicine is not contaminated. At the same time， medical staff may be exposed to risks such as cytotoxic drugs due to lack of protection. To solve the defects and deficiencies in intravenous infusion configuration， the “Dolphin 7” pharmacy intravenous compounding robots are introduced in our hospital， cluster management platform is constructed based on data middle platform service exchange system； mini-intelligent PIVAS module is designed and constructed. The mode can reduce the workload of medical staff， save medical construction and labor costs， also help to promote and deepen the construction of intelligent hospitals.

Smart Hip Ultrasound Technology in Screening for Infant Developmental Dysplasia of the Hip / 中山大学学报(医学科学版)

ObjectiveTo develop a deep learning system for early ultrasound screening of developmental dysplasia of the hip （DDH）， a new smart-hip ultrasound technique （S-hip）， and to validate its clinical application. MethodsWe selected 11，100 annotated and reviewed coronal ultrasound images of infant hips between November 2021 and August 2022， 8，100 of which were used for the training set and 3，000 for the test set， to build a S-hip deep learning system. To verify the consistency between the automated measurement by S-hip and the manual measurements by sonographers， 174 standard coronal ultrasound images of 87 infants' bilateral hips were acquired， then α angle， β angle and femoral head coverage （FHC） were measured by S-hip， an ultrasound expert and a resident. The measurement data and the time required for the measurements were recorded and statistically analyzed. Another 100 standard coronal ultrasound images of the hips were randomly selected and measured twice respectively by the ultrasound expert and resident to assess the intra-sonographer repeatability. ResultsThe intraclass correlation coefficient （ICC） （95% CI） values of α angle， β angle and FHC results measured by S-hip and ultrasound expert were 0.799 （0.738， 0.847）， 0.798 （0.737， 0.846） and 0.934 （0.954， 0.975）， respectively. Those values measured by the ultrasound expert and resident were 0.725 （0.645， 0.789）， 0.674 （0.583， 0.748） and 0.931 （0.908， 0.949）， respectively. The mean absolute errors （MAE） of α angle， β angle and FHC results between measurements by S-hip and ultrasound expert were 2.69 °， 4.43 ° and 2.47%， respectively. The time required for measurements by S-hip， ultrasound expert and resident was （1.59±0.36） s， （18.76±2.23） s and （19.45±2.76） s， respectively. The automated measurement by S-hip cost much shorter time than the manual measurements by sonographers and the difference was statistically significant （P<0.001）. The ICC （95% CI） values of α angle， β angle and FHC results between two measurements by the ultrasound expert were 0.943 （0.916， 0.961）， 0.959 （0.940， 0.972）， and 0.981 （0.971， 0.987）， respectively. Those values by the ultrasound resident were 0.884 （0.833， 0.921）， 0.921 （0.884， 0.946）， and 0.962 （0.944， 0.974）. ConclusionThe S-hip based on a deep learning system is a highly reliable automated technique to accurately measure α angle， β angle and FHC. Compared with ultrasound residents， S-hip allows for a more simplified and significantly quicker measurement， which may enhance the widespread use of hip ultrasound screening in infants.

Research advances in the clinical diagnosis and treatment of pheochromocytoma and paranganglioma / 现代泌尿外科杂志

Pheochromocytoma and paranganglioma (PPGL) is a rare neuroendocrine tumor. In recent years, the continuous development of multimodal imaging, pathonomics, genomics, transcriptomics, epigenomics, metabolism and proteomics have provided us with ideas to better understand the complex transfer mechanism of PPGL. This paper will review the precise typing system of PPGL, current research advances in the diagnosis and clinical prognosis.

Research progress of urethral sling in the treatment of male urinary incontinence after prostatectomy / 现代泌尿外科杂志

Stress urinary incontinence (SUI) following prostatectomy is an important and common problem in male, which can significantly reduce the quality of life. Urethral sling is a promising treatment for male SUI. It is easy to operate and can avoid the insertion of prosthesis, making it highly acceptable to patients. In recent years, with the advancement of technology, several kinds of slings have been put into clinical application and have achieved great outcomes. This article reviews the application of urethral sling in the treatment of SUI after prostatectomy.

Advances in the study of the m6A methyltransferase METTL3 promoting bladder cancer progression via AFF4/NF-κB/MYC signaling network / 现代泌尿外科杂志

Bladder cancer (BCa) is one of the most common cancers in urology,whose pathogenesis is still unclear. Methyltransferase-like 3(METTL3) is the most important part of N6-methyladenosine methyltransferase complex (m6A MTC),which mediates the methylation of mRNA to regulate the stability and translation process of mRNA. Researches have shown that METTL3 can promote BCa development via AFF4/NF-κB/MYC signaling network,which involves many kinds of signaling molecules. In addition,METTL3 can affect the expressions of AFF4,NF-κB and MYC,so as to affect their downstream signaling pathways and finally promote the malignant progression of tumor.

Research advances in the minimally invasive treatment of benign prostatic obstruction / 现代泌尿外科杂志

The number of benign prostatic obstruction (BPO) patients in China is increasing, and patients tend to be younger and younger. The former "gold standard" scheme of transurethral resection of the prostate (TURP) is more suitable for patients with prostate volume ranging from 40 mL to 80 mL, which may lead to excessive resection in patients with small prostate volume and low efficiency in patients with large prostate volume. New minimally invasive techniques have been introduced,including prostate artery embolization, laser surgery (such as holmium, green, diode, and thulium), minimally invasive simple prostatectomy, transperineal laser ablation, prostatic urethral lift,and robot-assisted water jet ablation of the prostate. These methods are alternatives to TURP and increasingly used in the treatment of BPO. This article reviewed the advances in minimally invasive treatment of BPO.

Research advances of urinary cell-free DNA in the detection and therapy of bladder cancer / 中华泌尿外科杂志

Bladder cancer is a common malignancy in the genitourinary system and the current therapeutic approaches are unsatisfactory. Urinary cell-free DNA (ucf DNA) has the ability to give comprehensive and crucial information on cancer as it carries genetic messages from cells shedding directly into urine as well as transporting from circulation. The ucf DNA of patients with bladder cancer carries disease information, suggesting that ucf DNA may have the ability to detect, monitor, and prognosticate patients with bladder cancer. The ucf DNA analysis bridges the gap between current techniques and enhances diagnostic and detection capabilities, and has a very promising future in term of translation into clinical practice. This article reviewed the progress of clinical applications of ucf DNA in bladder cancer.

Identification of Weak D Type 1 in Rh Blood Group System and Discussion of Transfusion Strategy / 中国实验血液学杂志

OBJECTIVE@#To investigate the molecular mechanism of one patient with abnormal serological phenotype in RhD and discuss the transfusion strategy.@*METHODS@#The RhD variant sample was screened from a patient with IgM type anti-D antibody and further determined by three different sources of anti-D antibodies. Ten exons and the adjacent introns of the RHD gene were amplified, purified and sequenced. RhCE phenotypes and RHCE genotypes were detected.@*RESULTS@#The patient with Rh variant showed abnormal results of serological tests. The RHD gene sequence analysis showed that the RHD*01W.01 with a variation (c.809T>G, p.Val270Gly) in exon 6 of the RHD gene was found in the patient. The RhCE phenotype was CcEe. The genotyping results of RHCE were consistent with the serological typing results.@*CONCLUSION@#The Rh variant of the patient is RHD*01W.01, these findings indicate that RhD variants should be analyzed by molecular assays for the sake of safe transfusion.

Epidemiological characteristics of current advanced schistosomiasis cases in Suzhou / 公共卫生与预防医学

Objective To understand the current situation of patients with advanced schistosomiasis in Suzhou, and to provide a basis for scientific management, medical assistance, and improvement of patients' quality of life. Methods Questionnaire survey, physical examination and B-ultrasound examination were performed on the registered patients with advanced schistosomiasis. The diagnosis and classification were carried out according to the “Schistosomiasis Control Manual”. The epidemiological and clinical characteristics, disease classification, and medical and financial assistance of all existing patients were analyzed. Results There were 2 420 cases of advanced schistosomiasis in Suzhou. Their distribution was highly correlated with the cumulative area of oncomelania snails and the cumulative number of schistosomiasis patients in each district (county) (r=0.949, P2=26.591, P2 =226.034, P<0.001), and the condition of patients with ascites was the worst. 1 438 patients' labor level was reduced, and 540 patients lost their labor ability, while only 442 patients were normal. Age increase (β=0.012，P<0.001), clinical classification being ascites type (β=0.346，P<0.001) and need for treatment (β=0.298，P<0.001) were risk factors for the loss of labor ability in patients with late schistosomiasis. The stable condition of the disease (β= -0.089，P=0.001) was a protective factor. Conclusion There are a large number of advanced schistosomiasis cases in Suzhou, and the epidemiological characteristics of advanced schistosomiasis patients in different districts (cities) are different. The relief work of advanced schistosomiasis in Suzhou should focus on the historical heavy epidemic areas, strengthen the nursing care of the elderly patients, and pay attention to the quality of life of patients with ascites. It is also important to strengthen the follow-up nursing of patients with splenomegaly to avoid turning into ascites. All districts and counties should be guided by the characteristics of local patients and formulate targeted scientific management methods and rescue policies to improve the quality of life of patients.

Study on the Identification of Samples Mistyped as O Phenotype and the Strategy of Safe Blood Transfusion / 中国实验血液学杂志

OBJECTIVE@#To investigate the indentification method of samples mistyped as O phenotype and to explore the precision transfusion strategy.@*METHODS@#The blood samples from donors and patients admitted in our center from 2018 to 2019 was collected. The samples with O phenotype suspected subtypes were further determined by tube test, adsorption-elution test, etc. Molecular testing was used to sequence the related blood type genes of the subjects.@*RESULTS@#Among 14 subjects misjudged as O, 11 different genotypes were identified, in which 3 blood donors were Ael02/O02, Bel03/O02, and one para-Bombay with B101/O02 (FUT1: h3h3; FUT2: Se@*CONCLUSION@#The phenotypes of Ael, Bel, Aw and para-Bombay subtypes are easily misjudged as type O. Molecular technology is helpful to identify the genotype of subtypes, and the corresponding transfusion strategies could be reasonably performed.

Different Subtypes Caused by c.721C>T Substitution in the Exon 7 of ABO Gene / 中国实验血液学杂志

OBJECTIVE@#To analyze the different subtypes caused by c.721C>T substitution in the exon 7 of the ABO gene, and to investigate the related molecular mechanism of different antigens expression.@*METHODS@#ABO subtypes in 7 samples were identified by standard serological methods. The exons 6, 7, and adjacent intron of ABO gene were amplified by Polymerase Chain Reaction (PCR), and the PCR products were analyzed by direct DNA sequencing and cloning sequencing.@*RESULTS@#ABO subtypes phenotypes were A@*CONCLUSION@#c.721C>T substitution in the ABO gene causes p.Arg241Trp exchange resulting in the decreasing of GTA or GTB activities and weaker antigen expression. O.01.07 is a null allele which cannot form a functional catalytic enzyme has no effect on A

Analysis of Reasons Causing False Positive of HBsAg Single-ELISA-Reactive in Blood Donors / 中国实验血液学杂志

OBJECTIVE@#To explore the reasons causing the false positive of HBsAg single-ELISA-reactive in blood donors of Jiangsu province so as to provide reference data for the return of blood donors.@*METHODS@#Serological test: HBsAg ELISA parallel detection was performed on 319 444 samples of blood donors from 2014 to 2017; the ECLIA was employed to confirm the single-ELISA-reactive (S/CO≥0.5) samples, the nucleic acid test was used to detect the HBV DNA on the all single-ELISA-reactive samples in 6/8 people mixed/single. Reagent evaluation: the Receiver-Operating-Characteristic curve (ROCC) was drawn by the ECLIA/NAT results as the gold standard, and the diagnostic performance of reagents A and B under different cut-off was evaluated.@*RESULTS@#A total of 227 (0.71‰) single-ELISA-reactive samples were detected among 319 444 blood donors, including 39 cases (17.2%) of positive HBsAg and 12 cases (5.3%) of positive HBV DNA; Under the maximum YI, the COI (1.0) employed by the manufacturer recommendation has a better diagnostic value than laboratory COI (0.5), and the capability of reagent A was better than that of reagent B (AUC: 0.661 vs 0.632; Youden: 0.329 vs 0.297), but the specificity of both reagents was restricted (＜60%). Under the maximum YI, the best cut-off value of reagents A and B were 2.4 and 1.4 COI, respectively. Compared with the cut-off value of manufacturer, the sensitivity of reagents A decreased by 33% and the false positive rate decreased by 60% while the sensitivity of reagent B increased by 140% and the false positive rate increased by 36%, respectively.@*CONCLUSION@#The false positive of HBsAg single-ELISA-reactive in blood donors is caused by the limited specificity of ELISA reagent and the setting of COI values. According to ROCC maximum YI method, the COI can be set as 2.4 COI and (0.5-1.4) COI for reagent A and B to reduce false positive rate.

Effect of Astragalus membranaceus on metabolic homeostasis of cardio-cerebrovascular system in mice / 中国药科大学学报

@#To explore the effect of Astragalus membranaceus, a traditional Chinese medicine, on metabolic homeostasis of heart, brain and blood in mice, and to elucidate the cardio-cerebrovascular protective mechanisms of AR from the perspective of metabolic regulation. Thirteen ICR male mice were randomly divided into two groups which were intragastrically administered with ultrapure water and aqueous extract of Astragalus membranaceus for 10 consecutive days, respectively. Liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) were used to comprehensively characterize the metabolic profiles of serum, heart and brain tissues. Multivariate statistical analysis combined with nonparametric tests were applied to screen and identify different metabolites, and then the related metabolic pathways were uncovered. Multivariate statistical analysis showed that the metabolic profiles of serum, heart, and brain tissues of mice after Astragalus membranaceus intervention significantly changed compared with the control group. A total of 15, 19, and 17 metabolites were identified in serum, heart, and brain tissues, respectively, among which palmitic acid and LysoPC (20∶3) were screened out from all types of biological samples. The results of metabolic pathway enrichment analysis showed that amino acid metabolism, phospholipid metabolism, fatty acid metabolism and tricarboxylic acid cycle were significantly affected. Astragalus membranaceus may protect the cardio-cerebrovascular system by regulating the metabolic homeostasis of amino acids, lipids and energy.

Dipeptidyl peptidase-4 promotes calcification of human vascular smooth muscle cells by inhibiting LincRNA ENST00000540293 expression / 中华内分泌代谢杂志

Objective To explore the molecular mechanism of dipeptidyl peptidase-4 ( DPP4) in the calcification of human vascular smooth muscle cells(HVSMCs). Methods The osteogenic differentiation of HVSMCs was induced by 200 ng/ ml DPP4 as calcification model. The differentially expressed long non-coding RNAs (lncRNAs) between DPP4 group and control group were analyzed by microarray, and the microarray results of LincRNA ENST00000540293 were validated by real-time PCR. After HVSMCs were incubated with LincRNA ENST00000540293 silencing positive reagent for 48 h, the expressions of calcification-related proteins osteoprotegerin (OPG) and bone morphogenetic protein 2(BMP-2) were detected by Western blotting and the formation of calcified nodules was observed by Alizarin red staining. Results The protein expressions of OPG and BMP-2 in HVSMCs were significantly increased after DPP4 intervention (P <0.05), with the increased formation of calcified nodules. RTqPCR showed that LincRNA ENST00000540293 expression was significantly decreased in DPP4 group as compared with the control group(P<0.05). The expressions of calcification-related proteins OPG and BMP-2 were significantly increased after LincRNA ENST00000540293 silence(P<0.05). Conclusion DPP4 may promote the calcification of HVSMC through inhibiting LincRNA ENST00000540293 expression.

Pharmacometabolomic prediction of individual differences of gastrointestinal toxicity complicating myelosuppression in rats induced by irinotecan

Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually, two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine.

Sero-prevalence of Babesia infection among voluntary blood donors in Jiangsu Province / 中国血吸虫病防治杂志

Objective To evaluate the sero-positivity of Babesia infection in voluntary blood donors in Jiangsu region, so as to provide the evidence for transfusion safety. Methods A total of 950 blood samples were collected from voluntary blood donors in Jiangsu Provincial Blood Center from February to May, 2017, and detected by double antigen sandwich ELISA targeting peptides derived from B. microti-secreted antigen 1 (BmSA1). The positive samples were confirmed by microscopy and nested-PCR to determine parasitemia. The prevalence of anti-BmSA1 was analyzed between/among different genders, ages and occupations of the blood donors. Results Of the 950 blood screened samples, 5 were positive for anti-BmSA1, and the sero-prevalence of Babesia infection was 0.53%. The 5 samples were all negative by microscopy and nested-PCR. There were no gender- (χ2 = 0.01, P =0.92) or age-specific differences (χ2 = 0.11, P = 0.95) in the sero-prevalence of Babesia infection; however, there was an occupation-specific difference detected in the sero-prevalence of Babesia infection (χ2 = 11.93, P < 0.05). Conclusion Babesia infection is detected in voluntary blood donors in Jiangsu region, which should be paid much attention.

Sero-prevalence of Babesia infection among voluntary blood donors in Jiangsu Province / 中国血吸虫病防治杂志

Objective To evaluate the sero-positivity of Babesia infection in voluntary blood donors in Jiangsu region, so as to provide the evidence for transfusion safety. Methods A total of 950 blood samples were collected from voluntary blood donors in Jiangsu Provincial Blood Center from February to May, 2017, and detected by double antigen sandwich ELISA targeting peptides derived from B. microti-secreted antigen 1 (BmSA1). The positive samples were confirmed by microscopy and nested-PCR to determine parasitemia. The prevalence of anti-BmSA1 was analyzed between/among different genders, ages and occupations of the blood donors. Results Of the 950 blood screened samples, 5 were positive for anti-BmSA1, and the sero-prevalence of Babesia infection was 0.53%. The 5 samples were all negative by microscopy and nested-PCR. There were no gender- (χ2 = 0.01, P =0.92) or age-specific differences (χ2 = 0.11, P = 0.95) in the sero-prevalence of Babesia infection; however, there was an occupation-specific difference detected in the sero-prevalence of Babesia infection (χ2 = 11.93, P < 0.05). Conclusion Babesia infection is detected in voluntary blood donors in Jiangsu region, which should be paid much attention.

Study on the Endocrine of Placenta and the Safety of Drugs Commonly Used During Pregnancy / 医药导报

Through exploring the role of placental endocrine,the relationship between placental endocrine changes and certain disease states,and the relationship between placental endocrine and rational use of drugs commonly used in pregnancy were summarized.Placental hormones play an important role during pregnancy.Placental endocrine abnormality can cause some diseases that may need drug treatment.Besides,some drugs also can affect the placenta endocrine,resulting in adverse pregnancy outcomes.Drug safety during pregnancy requires the consideration of the interaction between medicine and placenta endocrine.