Purity Assessment of Tripropyl Phosphate through Mass Balance and 1H and 31P Quantitative Nuclear Magnetic Resonance.

Tripropyl phosphate (TnPP) is a commonly used organic phosphate flame retardant in the textiles, plastics, and coating industries. Residues are commonly detected in samples from the environment and food. The availability of certified reference materials (CRMs) is essential to ensure the accuracy and traceability of detection results. In this study, a comprehensive characterization of a CRM for TnPP was carried out, and its purity was evaluated using two distinct methodologies: mass balance (MB) and quantitative nuclear magnetic resonance spectroscopy (qNMR). In the MB method, the levels of structurally related organic impurities are 1.37 mg/g. The water content was determined to be 3.16 mg/g, while inorganic impurities were found to be 0.87 mg/g, and no residual organic solvents were detected. Benzoic acid and monocrotophos were chosen as internal standards for 1H-qNMR and 31P-qNMR, respectively. The purity of the TnPP CRM was assessed as 994.6 mg/g, 994.1 mg/g, and 993.5 mg/g using MB, 1H-qNMR, and 31P-qNMR techniques, respectively. The verified purity of the TnPP CRM was ultimately determined to be 994.1 mg/g, with an expanded uncertainty of 3.4 mg/g (k = 2), ensuring traceability to the International System of Units (SI). This CRM can be effectively utilized for preparing calibration solutions suitable for the routine monitoring of TnPP residues in plastics and food samples.

Fragmentation Pathway of Organophosphorus Flame Retardants by Liquid Chromatography-Orbitrap-Based High-Resolution Mass Spectrometry.

Organophosphorus flame retardants (OPFRs) have been widely used in polymeric materials owing to their flame retardant and plasticizing effects. Investigating the fragmentation pathway of OPFRs is of great necessity for further discovering and identifying novel pollutants using orbitrap-based high-resolution mass spectrometry (HRMS). A total of 25 OPFRs, including alkyl, halogenated, and aromatic types, were analyzed in this study. The fragmentation pathways of the OPFRs were investigated using orbitrap-based HRMS with high-energy collision dissociation (HCD) in positive mode. The major fragmentation pathways for the three types of OPFRs are greatly affected by the substituents. In detail, the alkyl and halogenated OPFRs underwent three McLafferty hydrogen rearrangements, wherein the substituents were gradually cleaved to form the structurally stable [H4PO4]+ (m/z = 98.9845) ions. In contrast, the aromatic OPFRs would cleave not only the C-O bond but also the P-O bond, depending on the substituents, to form fragment ions such as [C6H7O]+ (m/z = 95.0495) or [C7H7]+ (m/z = 91.0530), among others. Using HRMS improved the accuracy of fragment ion identification, and the pathway became more evident. These fragmentation laws can provide identification information in pollutant screening work and theoretical references for the structural characterization of compounds with diverse substituent structures.

Atorvastatin Calcium Ameliorates Cognitive Deficits Through the AMPK/Mtor Pathway in Rats with Vascular Dementia.

AIM: In this study, the protective effects of atorvastatin calcium (AC) on nerve cells and cognitive improvement in vivo and in vitro were investigated by establishing cell models and vascular dementia (VD) rat models. BACKGROUND: VD is a neurodegenerative disease characterized by cognitive deficits caused by chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy and underlying mechanism are still unclear. OBJECTIVE: The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear. Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell model in vitro was established to investigate the function of AC in VD. METHODS: The spatial learning and memory abilities of rats were detected by the Morris method. The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in 4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the two groups was performed by Student's t-test. A two-way ANOVA test using GraphPad Prism 7 was applied for escape latency analysis and the swimming speed test. The difference was considered statistically significant at p < 0.05. RESULTS: AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals administered AC had considerably longer swimming times to the platform than VD rats. H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway. CONCLUSION: This study found that AC may relieve learning and memory deficits as well as neuronal damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating the AMPK/mTOR signalling pathway in neurons.

Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study.

Background: The purpose of this study was to compare the efficacy and safety of utidelone plus capecitabine for advanced first-line versus second-line or above therapy in metastatic breast cancer patients who had previously received anthracycline and taxane. At the same time, we compared the efficacy of utidelone plus capecitabine and vinorelbine plus cisplatin in advanced first-line treatment of metastatic breast cancer. Patients and methods: A retrospective cohort of 11 patients with metastatic breast cancer previously treated with anthracycline and taxane (including neoadjuvant and adjuvant therapies) for advanced first-line with utidelone plus capecitabine, 32 patients treated with second-line or above, and 60 patients with vinorelbine plus cisplatin between October 2011 and August 2022 was collected. The first and second groups were treated with utidelone plus capecitabine, and the third group was treated with vinorelbine plus cisplatin. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), objective response rate (ORR), and treatment safety. Results: By 03/31/2023, median PFS reached 11.70 months (95 % CI 0.093-0.141) in utidelone plus capecitabine group in the advanced first-line therapy, compared to 5.60 months (95 % CI 0.025-0.079) in the second-line or above therapy [HR 0.42, (95 % CI 0.226-0.787), P = 0.0077]. In utidelone plus capecitabine, the median OS was not reached in the advanced first-line therapy, with a mean overall survival of 23.16 months (95 % CI 0.198-0.265); whereas the median OS in the second-line or above therapy was 19.50 months (95 % CI 0.083-0.307), with a mean overall survival of 16.89 months (95 % CI 0.136-0.202) [HR 0.26, (95 % CI 0.098-0.678), P = 0.0495]. The ORR for advanced first-line therapy was 27.27 % (95%CI 0.060, 0.610) compared with 15.63 % (95%CI 0.053, 0.328) for second-line or above. In advanced first-line therapy, utidelone plus capecitabine was superior to vinorelbine plus cisplatin with a median PFS of 6.12 months (95 % CI 0.051-0.072) [HR 0.49, (95 % CI 0.286-0.839), P = 0.0291]. Compared with utidelone plus capecitabine, the median OS in vinorelbine plus cisplatin advanced first-line therapy group was 35.37 months (95 % CI 0.258-0.449), and the mean overall survival was 40.79 months (95 % CI 0.315-0.501) [HR 0.54, (95 % CI 0.188-1.568), P = 0.2587]. The ORR for vinorelbine plus cisplatin was 18.33 % (95 % CI 0.095, 0.304). The most common adverse events in our study were neurological toxicity, hand-foot syndrome, hematological toxicity, gastrointestinal toxicity, and hepatic and renal function abnormalities. There were no deaths due to adverse effects during the utidelone plus capecitabine treatment period. Conclusions: In MBC, advanced first-line therapy with utidelone plus capecitabine resulted in more favorable PFS, OS, and ORR than second-line or above therapy. In advanced first-line therapy, utidelone plus capecitabine had superior PFS, and ORR compared with vinorelbine plus cisplatin. This study concludes that utidelone plus capecitabine is a more valuable chemotherapy option in advanced first-line MBC.

[Screening of organophosphorus flame retardant residues in rice by QuEChERS-gas chromatography-quadrupole time-of-flight mass spectrometry].

Organophosphorus flame retardants (OPFRs) have emerged as good alternatives to brominated flame retardants, the use of which is globally restricted. In this study, a screening method based on QuEChERS-gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF/MS) was established for the determination of 21 OPFRs in rice. First, full scan (scanning range, m/z 50-450) was performed with a mixed standard solution of the 21 OPFRs (0.1 µg/g) by GC-Q-TOF/MS. The fragmentation pathways of these OPFRs were then investigated to explore their cleavage fragments, the interrelationships among fragments, and the possible cleavage modes of alkylated, chlorinated, and aromatic OPFRs. The retention times, isotopic abundance ratios, and molecular formulas of the characteristic fragments as well as the exact mass of the compounds were obtained to establish a mass spectral library of the OPFRs. Rice samples were extracted and purified by the QuEChERS method, and 0.5% formate acetonitrile solution was used as the extraction solvent; 4 g of magnesium sulfate, 1 g of sodium chloride, 0.5 g of disodium hydrogen citrate, and 1 g of sodium citrate as the extraction-salt combination; and 50 mg of primary secondary amine (PSA), 50 mg of octadecylsilane (C18), and 150 mg of magnesium sulfate as the purification materials. The chromatographic separation of the 21 OPFRs was completed within 16 min under optimized temperature program conditions on the DB-5MS UI column. The screening parameters were optimized, and a full scan of the samples was performed under the following conditions: number of characteristic fragment ions ≥2; accurate mass window=±2×10-5 (±20 ppm); retention time deviation=±0.2 min, and ion abundance deviation<20%. The developed method was applied to the screening 21 OPFRs in the samples. The results indicated that the matrix interference was greatly reduced by decreasing the extraction accurate mass window, thereby improving the signal-to-noise ratio of the analytes. The targets were extracted from the matrix interference and background noise using deconvolution software, which improved the match between the target compounds and the mass spectral library. The detection rates of alkyl and aromatic OPFRs increased by 22% and 25%, respectively, when the spiking level was increased from 2 to 10 ng/g. Among the chlorinated OPFRs, only tris(2-chloroisopropyl) phosphate (TCIPP) was not detected at a spiking level of 2 ng/g, indicating that chlorinated OPFRs could be identified even at low concentrations. The characteristic ions of the detected compounds matched those of the home-made mass spectral library well, indicating that the practical application of the home-made mass spectral library. The established screening method was applied in the determination of OPFRs in rice samples from different regions in China. A total of 11 OPFRs were detected, among which trimethyl phosphate (TMP), tri-iso-butyl phosphate (TiBP), and tris(3,5-dimethylphenyl) phosphate (T35DMPP) had the highest detection rates. These results indicate that these three OPFRs are widely used and can easily come into contact with rice samples through various routes. Differences in the types of OPFRs detected in the actual samples may be related to the types of OPFRs produced in local factories. OPFRs can be detected in rice samples by the developed GC-Q-TOF/MS screening method, which is helpful for the identification of OPFRs in complex matrix samples.

Influences and mechanism of erythropoietin on the cognitive function of vascular dementia rats.

PURPOSE: To investigate the influences and mechanism of erythropoietin (EPO) on the cognitive function of vascular dementia (VD) rats. METHODS: 1) Spatial memory capacity was assessed by Morris water maze test; 2) Pathological conditions of brain tissues were detected by hematoxylin-eosin (HE) staining; 3) The effect of treatment on apoptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining; 4) Western blotting was used to examine the protein expression in hippocampal neurons. RESULTS: The escape latency and swimming distance in the EPO group were much shorter than those in the Model group on the fifth day. In the spatial exploration test, the time spent in the target quadrant was longer, the number of platform crossings was larger and the swimming speed was higher in the Sham group and EPO group than those in the Model group. The results of HE staining showed that the cells in the hippocampal CA1 region were arranged closely in the Sham group, loosely and disorderly in the Model group but significantly better in the EPO group. Compared with that in the Model group, the number of apoptotic cells in the EPO group was obviously smaller. The results of Western blotting revealed that the expressions of EPO, p-EPOR, p-SHP2, p-TrKB, p-PI3K, p-ERK1/2 and Bcl-2 rose, while the expressions of P22, P47, Caspase-3, Caspase-9 and Bax significantly declined in the EPO group. CONCLUSIONS: EPO can effectively ameliorate the cognitive dysfunction induced by chronic hypoperfusion in VD rats by mediating oxidative stress-related pathways.

Accurate Determination of Trace Water in Organic Solution by Quantitative Nuclear Magnetic Resonance.

A new method accompanied by a derived equation for accurate determination of trace water was developed by using quantitative 1H nuclear magnetic resonance (qNMR) spectroscopy. Given that the response for each chemically distinct moiety is uniformly proportional to the number of the corresponding resonant nuclei within the analyte, it is practicable to directly quantify the water content via its proton number using qNMR. In this study, three water standards with known water contents (e.g., 10.02, 1.006, and 0.103 mg/g), which were accurately determined by a well-established Coulometric Karl Fischer (CKF) titration method, were measured by using the developed qNMR method. An excellent agreement between the results from these two methods was obtained. Then, the water content of Sudan I was determined by high-field NMR (HF-NMR) spectroscopy, and the water contents of acetone and bioethanol were measured by low-field NMR (LF-NMR) spectroscopy. These results were compared with the water content measured by the CKF method to confirm the applicability of the established qNMR method. The developed method can eliminate the influences of environmental humidity and background water in the solvent; subsequently, the results calculated by the derived equation were comparable to the nominal values. Under the optimal conditions, the limit of quantitation of this method was as low as 6.7 µg. The recommended sample sizes for practical samples with various water contents (e.g., 10.02, 1.006, and 0.103 mg/g) were determined to be 5, 50, and 60 mg, respectively, which are much smaller than those required for the CKF method. The new method has a static and stable process without any side reactions, and the traceability to the SI unit can be directly achieved through the NMR internal standard. This method overcomes the limitations of the CKF method, especially for measuring methanol-insoluble substances.

Effect of Kangfuxiaomi suppository on pelvic inflammatory disease in rats.

Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana, is a Traditional Chinese Medicine remedy widely used for the treatment of gynecological disorders. This study aimed to preliminarily explore the therapeutic effect of Kangfuxiaomi suppository in a rat model of PID established by chemical injury and pathogen infection. The key parameters assessed were vulvar inflammation score, vaginal + uterine organ index, and serum levels of interleukin (IL)- 8; tumor necrosis factor (TNF)-α; C-reactive protein (CRP); superoxide dismutase (SOD); and malondialdehyde (MDA). In addition, levels of IL-6, cyclooxygenase (COX)- 2, and IL-2 in cervical tissues as well as that of IL-1ß and prostaglandin E-2 (PGE2) in uterine tissues were measured. The expression levels of nuclear factor-kappa B (NF-κB) p65 and Toll-like receptor 4 (TLR4) in uterine tissues were detected by immunohistochemical method. After Kangfuxiaomi suppository treatment, the vulva inflammation score and histopathological score of PID rats showed a tendency to decrease. Serum IL-8, TNF-α, CRP, and MDA levels were reduced, while SOD levels were significantly increased. Levels of IL-6, IL-2, and COX-2 in cervical tissues were somewhat decreased, and PGE2 and IL-1ß levels in uterine tissue were significantly decreased. Moreover, the levels of NF-κB p65 and TLR4 protein expression were also decreased. These findings demonstrated the therapeutic effect of Kangfuxiaomi suppository in PID rats. The underlying mechanism may involve enhanced antioxidant capacity and decreased secretion of proinflammatory factors via the NF-κB/TLR4 signaling pathway.

[A Prediction Model for Human Immunodeficiency Virus Infection and Mother-to-Child Transmission Based on the Expression Levels of Selenoprotein Genes].

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.

Single-cell transcriptome sequencing of B-cell heterogeneity and tertiary lymphoid structure predicts breast cancer prognosis and neoadjuvant therapy efficacy.

BACKGROUND: Breast cancer (BC) is a highly heterogeneous disease, and although immunotherapy has recently increased patient survival in a number of solid and hematologic malignancies, most BC subtypes respond poorly to immune checkpoint blockade therapy (ICB). B cells, particularly those that congregate in tertiary lymphoid structures (TLS), play a significant role in antitumour immunity. However, B-cell heterogeneity at single-cell resolution and its clinical significance with TLS in BC need to be explored further. METHODS: Primary tumour lesions and surrounding normal tissues were taken from 14 BC patients, totaling 124,587 cells, for single-cell transcriptome sequencing and bioinformatics analysis. RESULTS: Based on the usual markers, the single-cell transcriptome profiles were classified into various clusters. A thorough single-cell study was conducted with a focus on tumour-infiltrating B cells (TIL-B) and tumour-associated neutrophils (TAN). TIL-B was divided into five clusters, and unusual cell types, such as follicular B cells, which are strongly related to immunotherapy efficacy, were identified. In BC, TAN and TIL-B infiltration are positively correlated, and at the same time, compared with TLS-high, TAN and TIL-B in TLS-low group are significantly positively correlated. CONCLUSIONS: In conclusion, our study highlights the heterogeneity of B cells in BC, explains how B cells and TLS contribute significantly to antitumour immunity at both the single-cell and clinical level, and offers a straightforward marker for TLS called CD23. These results will offer more pertinent information on the applicability and effectiveness of tumour immunotherapy for BC.

Anti-PD-1 therapy plus chemotherapy versus anti-PD-1 therapy alone in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia: a multicenter, retrospective study.

Background: Synergistic antitumor effects of immunotherapy and chemotherapy have been demonstrated in several solid tumors. However, this combination strategy has not been addressed in gestational trophoblastic neoplasia (GTN) cases. We therefore compared the safety and therapeutic effect of anti-programmed cell death 1 (PD-1) therapy combined with chemotherapy versus anti-PD-1 monotherapy among high-risk chemorefractory or relapsed GTN patients. Methods: This retrospective cohort study was conducted at three teaching hospitals in China. Chemorefractory or relapsed GTN cases receiving anti-PD-1 therapy combined with chemotherapy or anti-PD-1 monotherapy were selected from each center between August 2018 and March 2022. Study endpoints included objective response rate (ORR), treatment duration, overall survival (OS) and progression-free survival (PFS). The nature, prevalence and severity of treatment-related adverse events (TRAEs) were evaluated. Findings: This work enrolled 66 cases. Thirty-five and 31 patients received anti-PD-1 therapy alone and combined with chemotherapy, respectively. The combined treatment dramatically increased the objective response rate from 62.9% (22/35) to 96.8% (30/31) (p < 0.001). The median durations until complete response were 2.2 (interquartile range [IQR], 1.4-4.2) and 2.8 (IQR, 1.8-2.8) months in the anti-PD-1 monotherapy and combined treatment cohorts, respectively (P = 0.299). The complete response rate (CRR) for anti-PD-1-refractory patients to salvage chemotherapy was 84.6% (11/13). No significant difference in OS [HR 0.50 (95% CI 0.07-3.24), p = 0.499] was detected between anti-PD-1 cohort and anti-PD-1 plus chemotherapy cohort. The PFS in combined group was significantly longer than in anti-PD-1 group [HR 0.06 (95% CI 0.02-0.16), p < 0.001]. TRAEs were observed in 27 (77.1%) and 25 (80.6%) patients receiving anti-PD-1 therapy monotherapy and combined therapy, respectively (p = 0.729). Interpretation: Anti-PD-1 therapy combined with chemotherapy exhibits sustainably improved antitumor effect and tolerable toxic effects among high-risk chemorefractory or relapsed GTN cases. Patients not responding to PD-1 inhibitors can be effectively rescued with salvage chemotherapy. Funding: The study was supported by National Natural Science Foundation of China (81971475 and 81972451), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-083 and 2022-PUMCH-B-084).

ß-arrestin2 deficiency ameliorates S-100-induced autoimmune hepatitis in mice by inhibiting infiltration of monocyte-derived macrophage and attenuating hepatocyte apoptosis.

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. ß-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether ß-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and ß-arrestin2 knockout (Arrb2 KO) mice, and the experiments identified that liver ß-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, ß-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. ß-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that ß-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas ß-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, ß-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3ß pathway. These results suggest that ß-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, ß-arrestin2 may act as an effective therapeutic target for AIH.

Construction of a clinical nursing pathway for acute paraquat poisoning: Evidence-based research.

Aim: This study used the Delphi method and clinical expert discussions to develop an acute paraquat poisoning clinical nursing pathway to standardize acute paraquat poisoning nursing care. Background: In clinical practice, especially in basic-level hospitals, there is no unified standard pattern of treatment and nursing care for patients with paraquat poisoning. Methods: An extensive literature search was used to gather current clinical guidelines for treating paraquat poisoning which were then compiled into a Delphi expert letter of inquiry questionnaire which was sent to a panel of 12 experts. Results: A preliminary draft of the clinical nursing pathway table for acute paraquat poisoning with a standard hospitalization period of 21 days was established, with 6, 23, and 152 classes and I, II, and III indicators determined. The clinical nursing pathway table reduced the randomness of work, avoided nursing interruptions or omissions caused by negligence, and simplified the writing of nursing documents. Conclusions: The clinical nursing pathway can promote and improve the nursing care quality and management efficiency and has good clinical application value.

Investigating the Effects and Mechanism of Rhodiola Rosea Injection on Cardiac Function in Rats with Chronic Heart Failure.

AIM: To study the effect of Rhodiola Rosea injection on cardiac function and the reninangiotensin- aldosterone system (RASS) in rats with chronic heart failure. BACKGROUND: Rhodiola Rosea injection, a traditional Chinese medication for relieving blood stasis and improving blood circulation, is an excellent therapeutic for treating coronary heart disease-angina pectoris. Rhodiola Rosea injection's major component, salidroside, protects the cardiovascular system. But there isn't much first-hand evidence about how injectable Rhodiola Rosea affects heart failure. OBJECTIVES: In this study, a rat model of heart failure was established, and the effect of Rhodiola rosea injection on myocardial cell morphology, cardiac function, and ventricular remodelling in rats with heart failure was investigated. METHODS: 66 SD male rats were selected; 10 were randomly selected as a blank control group, and 56 were treated intraperitoneally with doxorubicin (4 g/g). After 6 weeks, all animals had LVEF 60%. Established a heart failure model. Each group had 14 rats: model control, low-dose, mediumdose, and high-dose Rhodiola Rosea injection. The 2 mL/kg of Rhodiola Rosea injection was injected into the tail vein once a day for 2 weeks. Both the blank and control groups received normal daily saline. After 2 weeks, the echocardiographic index, RASS-related index, and serum BNP level were assessed in all rats, and myocardial tissue morphology was observed. MiRNA423-5p, miRNA499-5p, and miRNA210-3p were extracted from peripheral blood. Rhodiola rosea injection on its expression was compared to healthy control rats. RESULTS: 6 mL/kg Rhodiola Rosea injection lowered LVEDV and LVESV while increasing LVEF and LVFS. Injections of 6 mL/kg Rhodiola Rosea reduce plasma levels of miR-210-3p, miR-423- 5p, miRNA-499, and BNP in heart failure model rats. The 6 mL/kg Rhodiola Rosea injection can restore the RASS indexes of heart failure rats to the level of the normal group. CONCLUSION: The present study offers preliminary evidence supporting the use of Rhodiola Rosea injection in the treatment of heart failure and offers a solid foundation for clinical off-label medication use.

Novo pathogenic variations of NLRP7 increasing the risk of gestational trophoblastic neoplasia.

Identification of novo mutations of NLRP7 in HM patients. NLRP7 mutations increasing the risk of HM progression.

Comparing the application of three thrombosis risk assessment models in patients with acute poisoning: A cross-sectional survey.

Background: Patients with acute toxic hemoperfusion are prone to deep vein thrombosis. However, there is no risk assessment model for thrombosis in patients with acute toxic hemoperfusion. Therefore, we compared three commonly used risk assessment models for deep vein thrombosis to determine the model most suitable for assessment of deep vein thrombosis in patients with acute toxic hemoperfusion. Methods: Caprini, Autar, and Padua thrombosis risk assessment models were used to assess the risk of deep vein thrombosis in patients with acute poisoning and hemoperfusion admitted to a grade A hospital in Shandong province from October 2017 to February 2019. The predictive values of the three models were compared using receiver operating characteristic (ROC) curve analysis. Results: The risk assessment model scores of Caprini, Autar, and Padua were 7.55 ± 1.76, 8.63 ± 2.36, and 3.92 ± 0.55, respectively. The Caprini risk assessment model was significantly different (p < 0.05) in high-risk patients in the thrombus and non-thrombotic groups; the difference between the other two models was not significant (p > 0.05). The areas under the ROC curve of the Caprini, Autar, and Padua risk assessment models were 0.673, 0.585, and 0.535, respectively. The difference in areas under the ROC curve between the Caprini risk assessment model and the Autar risk assessment model as well as the Padua risk assessment model was significant (p < 0.05), but the areas under the ROC curve of the Autar risk assessment model and the Padua risk assessment model were not statistically significant (p > 0.05). The Caprini risk assessment model had a sensitivity of 91.9%, specificity of 33.1%, and a Youden index of 0.249. The sensitivity and specificity of Autar's risk assessment model were 37.0 and 77.2%, respectively, and the Youden index was 0.141. The Padua risk assessment model had a sensitivity of 91.3%, specificity of 15.0%, and a Youden index of 0.063. Conclusion: The three thrombosis risk assessment models were not suitable for patients with acute poisoning and hemoperfusion.

CP-25 exerts a protective effect against ConA-induced hepatitis via regulating inflammation and immune response.

Hepatitis is a complex multifactorial pathological disorder, which can eventually lead to liver failure and even potentially be life threatening. Paeoniflorin-6'-O-benzene sulfonate (CP-25) has proven to have critical anti-inflammatory effects in arthritis. However, the effects of CP-25 in the pathogenesis of hepatitis remains unclear. In this experiment, mice were intragastrically administered with CP-25 (25, 50 and 100 mg/kg), and then ConA (25 mg/kg) was intravenous injected to establish hepatitis model in vivo. CP-25 administration attenuated liver damage and decreased ALT and AST activities in mice with hepatitis. Besides, CP-25 modulated immune responses including down-regulated the proportions of activated CD4+, activated CD8+ T cells, and ratio of Th1/Th2 in ConA-injected mice. Furthermore, ConA-mediated production of reactive oxygen species (ROS), release of inflammatory cytokines including IFN-γ, TNF-α, activation of MAPK pathways and nuclear translocation of nuclear factor-kappaB (NF-κB) were significantly decreased in CP-25 administrated mice. In ConA-stimulated RAW264.7 cells, CP-25 suppressed inflammatory cytokines secretion and reduced ROS level, which were consistent with animal experiments. Otherwise, the data showed that CP-25 restrained phosphorylation of ERK, JNK and p38 MAPK pathways influenced by ROS, accompanied with inhibiting NF-κB nuclear translocation. In conclusion, our findings indicated that CP-25 protected against ConA-induced hepatitis may through modulating immune responses and attenuating ROS-mediated inflammation via the MAPK/NF-κB signaling pathway.

Stability Evaluation of Aflatoxin B1 Solution Certified Reference Material via Ultra-High Performance Liquid Chromatography Coupled with High-Resolution Mass Spectrometry.

Aflatoxin B1 (AFB1) solution certified reference materials (CRMs) have been widely utilized in the measurements of AFB1 contaminations in foods and agricultural products. It is of great importance to evaluate the stability of AFB1 solution CRMs in different matrices for their practical applications. In this study, the stability of AFB1 solution CRM was investigated and its degradation products under various conditions were elucidated using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry for the first time. Exposure to high temperatures and UV light irradiation accelerated the degradation of AFB1 solution significantly, and the degradation products were largely dependent on the solvents. Two degradation pathways were proposed based on the degradation products. The addition reaction, oxidation reaction, and modification of the methoxy group are the major processes involved in the degradation of the AFB1 solution. The results of this study indicate that the property value of the acetonitrile solution of AFB1 can be well retained when it is stored at temperatures lower than 60 °C, and the exposure to UV light irradiation is avoided.

Effectiveness and Safety of Toripalimab Combination Therapies for Patients With Chemo-Resistant Choriocarcinoma.

Toripalimab as a novel PD-1 inhibitor has presented its promising efficacy in patients who developed chemo-refractory carcinomas, whereas no study has ever investigated the effectiveness of toripalimab in chemo-resistant choriocarcinoma. Here we reported the effectiveness and safety data of 4 patients with chemo-resistant choriocarcinoma who underwent PD-1 antibody therapy by toripalimab and individualized chemotherapies. From January 2019 to August 2020, 4 patients with choriocarcinoma were admitted in Shengjing Hospital of China Medical University. The patients' age ranged from 29 to 52 years with a median of 36 years. All the patients achieved CR after the combined therapy of toripalimab with individualized chemotherapies according to the decreased serum ß-hcg level. Two of the four patients were observed with treatment-related adverse events (AEs), including one grade I skin rash and one grade I pruritus. Our cases showed that toripalimab combined with chemotherapy presented a tolerable safety profile and promising effectiveness in patients with chemo-resistant choriocarcinoma, indicating its potential as salvage therapy for this subset of patients.

Pre-diagnostic dietary consumption of calcium and magnesium and calcium-to-magnesium intake ratio and ovarian cancer mortality: results from the ovarian cancer follow-up study (OOPS).

PURPOSE: Previous studies have indicated that dietary consumption of calcium (Ca), magnesium (Mg), and the Ca-to-Mg (Ca:Mg) ratio were associated with different health outcomes. However, no study has evaluated the association of pre-diagnostic Ca, Mg, and Ca:Mg ratio consumption with ovarian cancer (OC) survival. METHODS: The aforementioned associations were investigated in a cohort of 853 Chinese women diagnosed with OC between 2015 and 2020. A validated food frequency questionnaire was used to evaluate pre-diagnostic diet information. Deaths were recorded until March 31, 2021 via medical records and active follow-up. Cox proportional hazards model was applied to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 130 deaths were observed during a median follow-up of 37.2 months. After adjustment for potential confounders, pre-diagnostic Ca (HR< 600 vs. > 1000 = 1.45, 95% CI = 0.47-4.46, p for trend = 0.69) and Mg (HR< 250 vs. > 330 = 0.90, 95% CI = 0.39-2.08, p for trend = 0.77) intakes were found to be unrelated to OC survival, whereas a higher Ca:Mg intake ratio was significantly associated with worse survival (HR< 1.7 vs. > 2.5 = 2.72, 95% CI = 1.28-5.78, p for trend < 0.05). A significant result was also observed when treating the Ca:Mg ratio as a continuous variable (HR = 1.69, 95% CI = 1.12-2.55) for one-unit increment. CONCLUSION: Pre-diagnostic consumption of Ca and Mg was unrelated to OC survival, while a higher Ca:Mg intake ratio was strongly associated with worse survival among OC patients.