Objective: To establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method based on solid-phase extraction column purification for simultaneous determination of cyromazine and melamine in poultry eggs and meat. Methods: Eggs, quail eggs, and chicken were collected from markets. After homogenization, the sample was extracted with 0.5% formic acid in acetonitrile, subjected to solid-phase extraction using an MCX cartridge, and eluted with 5% ammonia in methanol. The eluate was collected, evaporated to near dryness under nitrogen, and reconstituted in a 10% aqueous methanol solution. Separated using TSK gel Amide-80 column (2.0 mm×150 mm, 5 μm), cyromazine and melamine were simultaneously detected in positive ion multiple reaction monitoring mode via tandem mass spectrometry, with quantification achieved by isotope dilution internal standard methods. Efficiency was enhanced and matrix interference minimized by optimizing conditions such as sample extraction, solid-phase extraction cartridge selection, and instrumental parameters. Calibration curves were constructed, and detection limits, quantification limits, spiked recoveries, and relative standard deviations for (RSD) of cyromazine and melamine were calculated. Results: After method optimization, matrix effects for cyromazine and melamine ranged from 0.97 to 1.04, indicating no significant matrix suppression or enhancement. Both cyromazine and melamine exhibited excellent linearity within the concentration range of 1.0-200.0 ng/mL, with correlation coefficients ≥0.999 5. The limits of detection were 0.3 μg/kg for cyromazine and 0.5 μg/kg for melamine, the quantification limits were 1.0 and 1.5 μg/kg, respectively. At spiked levels of 1.0, 20.0, and 150.0 μg/kg, the average recoveries ranged from 78.6% to 103.1%, with RSD between 3.5% and 6.3%. Among 95 samples tested, cyromazine was detected in 6 samples and melamine in 5 samples; neither cyromazine nor melamine was detected in chicken samples. Conclusion The UPLC-MS/MS method established in this study enables simultaneous detection and accurate quantification of cyromazine and melamine in poultry eggs and meat.

Fertility preservation technology provides an effective method for protecting the reproductive resources of patients with malignant tumors.At the same time,it is inevitable to face great ethical dilemmas in the process of technological implementation.From an ethical perspective,this paper sorted out the research on fertility preservation in tumor patients abroad,as well as analyzed the ethical issues faced by tumor patients in the communication decision-making and implementation stages of fertility protection.Specifically,these included informing and discussing the reproductive information and preservation choices of tumor patients,fertility decision-making of adolescent tumor patients,psychological support for fertility in tumor patients,ownership and use rights of reproductive materials and their disposal methods,fairness in the allocation of social health resources and other ethical issues.Combining with the actual situation in China,this paper further discussed how to put forward corresponding countermeasures based on following ethical principles such as favorable without harm,informed consent,cautious application,and ethical supervision,with a view to promoting the further development and application of fertility preservation technology in clinical practice.

Using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.

Fabry disease is a X-linked inherited lysosomal storage disease. The pathogenesis is that mutations in the GLA gene lead to the decrease or lack of α-galactosidase A activity, followed by the accumulation of substrate and its intermediate metabolites in cells and tissues, eventually leading to multiple organ injury. The rise of specific treatment and gene technology pushes the application of precision medicine in patients with Fabry disease. As a milestone in the specific treatment of Fabry disease, enzyme replacement therapy can delay disease progression and improve quality of life, but not all carriers with GLA mutation need intervention immediately, and indeed individualized treatment is required. However, enzyme-enhanced therapy is only suitable for "amenable mutations" and has clinical application limitation. Therefore, new treatments such as substrate reduction therapy, second-generation enzyme replacement therapy, and gene therapy are already undergoing clinical trials, expected to bring new gospel to Fabry disease patients. This article will review development of precision treatment on Fabry disease, providing the basis of individualized treatment for the drug selection and prevention of side effect. The expectation is to drive future therapeutic strategies toward precision-based treatment.

Divisions at the periphery and midzone of mitochondria are two fission signatures that determine the fate of mitochondria and cells.Pharmacological induction of excessively asymmetric mitofission-associated cell death(MFAD)by switching the scission position from the mitochondrial midzone to the periphery represents a promising strategy for anticancer therapy.By screening a series of pan-inhibitors,we identified pracinostat,a pan-histone deacetylase(HDAC)inhibitor,as a novel MFAD inducer,that exhibited a significant anticancer effect on colorectal cancer(CRC)in vivo and in vitro.Pracinostat increased the expression of cyclin-dependent kinase 5(CDK5)and induced its acetylation at residue lysine 33,accelerating the formation of complex CDK5/CDK5 regulatory subunit 1 and dynamin-related protein 1(Drp1)-mediated mitochondrial peripheral fission.CRC cells with high level of CDK5(CDK5-high)displayed midzone mitochondrial division that was associated with oncogenic phenotype,but treatment with pracinostat led to a lethal increase in the already-elevated level of CDK5 in the CRC cells.Mechanistically,pracinostat switched the scission position from the mitochondrial midzone to the periphery by improving the binding of Drp1 from mitochondrial fission factor(MFF)to mitochondrial fission 1 protein(FIS1).Thus,our results revealed the anticancer mechanism of HDACi pracinostat in CRC via activating CDK5-Drp1 signaling to cause selective MFAD of those CDK5-high tumor cells,which implicates a new paradigm to develop potential therapeutic strategies for CRC treatment.

Objective:To explore the application of cognitive interview (CI) in intercultural adaptation of the Happiness Scale for Middle-Aged Women (HAS-MW) .Methods:This was a qualitative study. In January 2022, 20 middle-aged women in community of Yanji City were selected by purposive sampling for two rounds of CI, and 10 subjects participated in each round of CI. According to the interview outline, we understood the understanding of the subjects on the HAS-MW items that were preliminarily localized in Chinese. The expert group discussed and revised the items of the scale according to the interview results.Results:In this study, a total of 2 rounds of cognitive interviews were conducted, the age of 10 respondents (P1-P10) in the first round was (49.00±3.55) , and the age of 10 respondents (P11-P20) in the second round was (51.00±3.16) . After the first round, 6 items in HAS-MW were revised due to "imperfect language, grammar and expression". The second round of CI results showed that the respondents understood the contents of the revised scale items and believed that they were consistent with the original scale.Conclusions:Through CI, we can comprehensively understand middle-aged women's understanding of the content of the HAS-MW, effectively find out the cognitive bias caused by improper language expression in the process of the scale's localization, improve the understanding of the content of the scale by the interviewees, which is conducive to intercultural adaptation of the HAS-MW and provides a reference for the revision of the scale.

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

OBJECTIVE: To study the cytokine patterns in patients with rheumatoid arthritis (RA) and healthy individuals and identify candidate serum biomarkers for clinical diagnosis of RA. METHODS: This study was conducted among 59 patients diagnosed with RA in our hospital from 2015 to 2019 with 46 age- and gender-matched healthy subjects who received regular physical examinations in our hospital as the control group. Serological autoimmune profiles of 5 RA patients and 5 healthy control subjects were obtained from human cytokine microarrays. We selected 4 differentially expressed cytokines (LIMPII, ROBO3, Periostin and IGFBP-4) and 2 soluble cytokine receptors of interest (2B4 and Tie-2) and examined their serum levels using enzyme-linked immunosorbent assay in 54 RA patients and 41 healthy control subjects. Spearman correlation test was performed to assess the correlation of serum cytokine and soluble receptor expression levels with the clinical features including rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score (DAS28) and health assessment questionnaire (HAQ). Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic capability of these cytokines. RESULTS: We identified 6 dysregulated cytokines and soluble receptors (2B4, LIMPII, Tie-2, ROBO3, periostin and IGFBP-4) in RA patients (P < 0.01). The serum levels of LIMPII, ROBO3 and periostin were significantly correlated with the disease activity indicators including RF (P < 0.001), CRP (P < 0.001), DAS28 (P < 0.001) and HAQ (P < 0.001) in RA patients. Among the 6 candidate cytokines, 2B4 showed the largest area under the curve (AUC) of 0.861 for RA diagnosis (P < 0.001), followed then by LIMPII, ROBO3, periostin, Tie-2 and IGFBP-4. CONCLUSION Serum levels of LIMPII, ROBO3 and periostin can be indicative of the disease activity of RA, and serum 2B4, LIMPII, periostin, ROBO3, IGFBP-4 and Tie-2 levels may serve as biomarkers for the diagnosis of RA.
Arthritis, Rheumatoid/diagnosis* ; Biomarkers ; C-Reactive Protein ; Cytokines ; Humans ; Insulin-Like Growth Factor Binding Protein 4 ; Protein Array Analysis ; Receptors, Cell Surface

Objective:To establish a IgA nephropathy (IgAN) standard dataset for the structured and standardization of IgAN clinical information, which will be beneficial to the integration and utilization of clinical information among different medical institutions. Therefore, the IgAN Expert Collaboration Group composed the "IgA Nephropathy Standard Dataset".Methods:Referring to the domestic information standards, guidelines, data standard and consensus of related fields, based on electronic medical history, the patient identification number was used as the primary key of the system to collect information. By standardizing each data element in the data set, the standardization of the management system in data and information exchange, data collaboration and sharing was ensured, and a quality control system was developed.Results:This standard dataset included 607 data elements and 8 business domains, which were patient information, medical history information, physical examination, laboratory examination, assistant examination, renal pathology, drug treatment, and follow-up, respectively. Each module was composed of module name, data element name, English name, definition, range, reference standard, etc. At the same time, a corresponding quality control system was formulated to evaluate data quality from multiple dimensions such as completeness, standardization, accuracy, timeliness, and security for ensuring the high quality and security of the data.Conclusion:The IgAN standard dataset is established, which will contribute to the structuration and standardization of clinical information of IgAN patients.

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.
China ; Drugs, Chinese Herbal ; Humans ; Hypertension, Pulmonary/drug therapy* ; Materia Medica ; Medicine, Chinese Traditional