Effects of intravenous nicardipine followed by oral labetalol in combination with nifedipine controlled-release tablet on severe peripartum hypertension.

OBJECTIVES: To investigate the effects of intravenous nicardipine as initial therapy and oral labetalol combined with nifedipine controlled-release tablet as subsequent treatment of severe peripartum hypertension. MATERIAL AND METHODS: Intravenous nicardipine was delivered as the initial treatment, after the target blood pressure (BP) had been achieved, oral labetalol was used to maintain the target BP. If oral labetalol failed to maintain the target BP, oral labetalol combined with nifedipine controlled-release tablet was used. RESULTS: A total number of 131 patients were enrolled. The target BP (BP < 140/90 mmHg) was achieved in all patients within 60 minutes by intravenous nicardipine. After receiving labetalol orally, the target BP was maintained in nine patients. However, in 104 patients, we had to combine oral labetalol and nifedipine controlled-release tablet due to re-elevation of their systolic BP to 140-159 mmHg. In 18 patients, we restarted intravenous nicardipine because their systolic BP re-elevated above 160 mm Hg. Among the 104 patients who received oral labetalol and nifedipine controlled-release tablet, the target BP was achieved and maintained in 96 patients, and eight patients had to restart nicardipine. Of the total number of 26 patients in whom intravenous nicardipine was resumed, the target BP was successfully maintained in 22 patients with oral labetalol combined with nifedipine controlled-release tablet. CONCLUSIONS: Intravenous nicardipine rapidly and safely lowered severe peripartum hypertension. As subsequent therapy, oral labetalol combined with nifedipine controlled-release tablet protocol may be applied to effectively maintain a target BP.

Inhibition of canine parvovirus 2 (CPV-2) replication by TAT-scFv through targeting of the viral structural protein VP2 of CPV-2.

Canine parvovirus (CPV) causes severe infectious disease with a high mortality rate in dogs. CPV is still a major health issue of dogs in the clinic. Therefore, there is an urgent need to develop effective drugs to treat the disease. In this study, we fused the transactivating transcriptional activator peptide (TAT) with scFv. TAT-scFv was identified by Western blot. CCK8 kit was used to detect the toxicity of TAT-scFv to cells. The binding activity of TAT-scFv to CPV-2-VP2 was detected by DAS ELISA. The cell uptake rate of TAT-scFv was assessed by IFA. After infection with CPV-2, F81 cells were incubated by TAT-scFv. The replication of virus was measured to determine the neutralization effect of TAT-scFv on intracellular and extracellular viruses. Protein docking was used to predict the amino acid (AA) sites of VP2 binding to TAT-scFv. TAT-scFv was expressed in Escherichia coli and purified. The DAS ELISA showed that TAT-scFv could bind with CPV-2-VP2. We demonstrated that TAT-scFv entered cells in a dose-dependent and time-dependent manner and effectively inhibited the replication of CPV-2. Using protein docking, we determined the interaction pattern and found that the N-terminal region (AA 41-49) and the C-terminal region (AA 558) of VP2 interacted with the TAT-scFv. Taken together, these results suggest that, TAT-scFv may be a potential antiviral drug for inhibiting CPV-2 replication and controlling disease caused by CPV-2.

Motility-related microRNAs identified in pig seminal plasma exosomes by high-throughput small RNA sequencing.

Boar fertility is a key determinant of the production efficiency of the whole pig breeding industry and boar sperm motility is the seminal parameter with the greatest impact on the fecundity of a sow. Exosomes are small, extracellular vesicles found in many body fluids. Seminal plasma exosomes, which are secreted by the epididymis, prostate, seminal vesicles, and testes, contain a large number of miRNAs, the types and levels of which can reflect the physiological state of source cells. It has been shown that the expression profile of seminal plasma exosomal miRNA differs between low-motility semen and normal semen. The aim of this study was to investigate the relationship between semen motility and exosomal miRNA profiles to obtain information that would allow to predict boar fertility, as well as contribute to the understanding of the mechanisms by which exosomal miRNAs regulate semen motility. Three high-motility (semen motility >90 %) and three low-motility (semen motility <80 %) semen samples were collected from Landrace and Yorkshire boars, respectively, and seminal plasma exosomes were extracted by ultracentrifugation. Exosome characterization was performed using transmission electron microscopy, NTA, and Western blot. The expression profiles of exosomal miRNAs associated with semen motility in the two boar breeds were subsequently determined by small RNA sequencing. The results showed that 297 known miRNAs and 295 novel RNAs were co-expressed in the four groups. Notably, six miRNAs (ssc-miR-122-5p, ssc-miR-486, ssc-miR-451, ssc-miR-345-3p, ssc-miR-362, and ssc-miR-500-5p) were found to be differentially expressed in both boar breeds. Enrichment analysis of the target genes of the differentially expressed miRNAs showed that they were mainly involved in biological processes such as regulation of transcription from RNA polymerase II promoter, regulation of gene expression, and intracellular signal transduction and signaling pathways such as the PI3K-Akt, MAPK, and Ras signaling pathways. The six differentially expressed miRNAs identified in this study have significant potential as noninvasive markers of boar semen motility. Meanwhile, the results of the enrichment analysis provide novel insights into the mechanisms underlying the regulation of semen motility.

Research progress on the effects of gut microbiome on lung damage induced by particulate matter exposure.

Air pollution is one of the top five causes of death in the world and has become a research hotspot. In the past, the health effects of particulate matter (PM), the main component of air pollutants, were mainly focused on the respiratory and cardiovascular systems. However, in recent years, the intestinal damage caused by PM and its relationship with gut microbiome (GM) homeostasis, thereby affecting the composition and function of GM and bringing disease burden to the host lung through different mechanisms, have attracted more and more attention. Therefore, this paper reviews the latest research progress in the effect of PM on GM-induced lung damage and its possible interaction pathways and explores the potential immune inflammatory mechanism with the gut-lung axis as the hub in order to understand the current research situation and existing problems, and to provide new ideas for further research on the relationship between PM pollution, GM, and lung damage.

Parallel evolution of two AIM24 protein subfamilies and their conserved functions in ER stress tolerance in land plants.

Despite decades of efforts in genome sequencing and functional characterization, some important protein families remain poorly understood. In this study, we report the classification, evolution, and functions of the largely uncharacterized AIM24 protein family in plants, including the identification of a novel subfamily. We show that two AIM24 subfamilies (AIM24-A and AIM24-B) are commonly distributed in major plant groups. These two subfamilies not only have modest sequence similarities and different gene structures but also are of independent bacterial ancestry. We performed comparative functional investigations on the two AIM24 subfamilies using three model plants: the moss Physcomitrium patens, the liverwort Marchantia polymorpha, and the flowering plant Arabidopsis thaliana. Intriguingly, despite their significant differences in sequence and gene structure, both AIM24 subfamilies are involved in ER stress tolerance and the unfolded protein response (UPR). In addition, transformation of the AIM24-A gene from P. patens into the AIM24-B null mutant of A. thaliana could at least partially rescue ER stress tolerance and the UPR. We also discuss the role of AIM24 genes in plant development and other cellular activities. This study provides a unique example of parallel evolution in molecular functions and can serve as a foundation for further investigation of the AIM24 family in plants.

A risk score for early predicting bloodstream infections in febrile obstetric patients: a pilot study.

PURPOSE: Early prediction of bloodstream infections (BSI) among obstetric patients remains to be a challenge for clinicians. The objective of this study was to develop a risk score and assess its discriminative ability in febrile obstetric patients in a maternal intensive care unit (ICU). METHODS: Between May 2015 and August 2020, a total of 497 febrile obstetric patients were categorized into BSI group (n = 276) and Non-BSI group (n = 221) based on the result of blood cultures. White blood cell count, C-reactive protein (CRP), procalcitonin (PCT), time of interval from amniorrhea to fever (IFAF) and maximum body temperature (Tmax) were compared between the two groups. All patients were divided into training set (n = 298) and validation set (n = 199). The risk score was established using univariate and multivariate logistic regression from patients in the training set, and its discriminative ability was tested among patients in the validation set. RESULTS: The levels of neutrophil, CRP, PCT, IFAF and Tmax were significantly higher in BSI group than those in Non-BSI group. PROM, Tmax, neutrophil and CRP acted as independent predictive factors for BSI in the training set. The area under the receiver operating characteristic curve of risk score for early prediction of BSI in the training, validation set and the whole population was 0.829 (95% CI 0.783-0.876), 0.848 (95% CI 0.792-0.903) and 0.838 (95% CI 0.803-0.873), respectively. CONCLUSION: The risk score has a feasible discriminatory ability in early prediction of BSI in febrile obstetric patients.

Metabolomic analysis reveals spermatozoa and seminal plasma differences between Duroc and Liang guang Small-spotted pig.

The Liang guang Small-spotted pig is a well-known Chinese indigenous pig that is valued for its exceptional meat quality. However, the Liang guang Small-spotted pig has a lower semen storage capacity, shorter storage time and worse semen quality compared to Duroc. Pig sperm used for artificial insemination (AI) loses part of vitality and quality when being stored in commercial solutions. Serious vitality losses and short shelf life of the semen are particularly prominent in Liang guang Small-spotted pig. In this study, the metabolites in seminal plasma and spermatozoa of Duroc and Liang guang Small-spotted pigs were identified using UHPLC-Q-TOF/MS technology. The findings indicated forty distinct metabolites concentrating on energy metabolic substrates and antioxidant capacity in Liang guang Small-spotted pig and Duroc seminal plasma, including D-Fructose, succinate, 2-dehydro-3-deoxy-d-gluconate, alanine betaine, citrate, carnitine, acetylcarnitine and so on. Seventeen different metabolites were explored, with a focus on glycerophospholipid metabolism in Liang guang Small-spotted pig and Duroc spermatozoa, primarily including glycerol 3-phosphate, acetylcarnitine, phosphatidylcholine (PC) 16:0/16:0, palmitoyl sphingomyelin, acetylcholine, choline, glycerophosphocholine, betaine, L-carnitine, creatinine and others. This study reveals the metabolite profile of spermatozoa and seminal plasma among different pig breeds and might be valuable for understanding the mechanisms that lead to sperm storage capacity. Metabolites involved in energy metabolism, antioxidant capacity and glycerophospholipid metabolism might be key to the poor sperm storage capacity in Liang guang Small-spotted pig.

The potential value of LC-MS non-targeted metabonomics in the diagnosis of follicular thyroid carcinoma.

Background: To explore the metabolic differences of follicular thyroid carcinoma (FTC) by metabonomics, to find potential biomarkers for the diagnosis of FTC, and to explore the pathogenesis and diagnosis and treatment strategies of FTC. Method: The metabonomics of 15 patients with FTC and 15 patients with follicular thyroid nodules(FTN) treated in Henan Cancer Hospital were analyzed by liquid chromatography-mass spectrometry (LC-MS). Results: The analysis showed that the metabolite profiles of FTC tissues could be well distinguished from those of control tissues, and 6 kinds of lipids were identified respectively, including lysophosphatidic acid(LysoPA) [LysoPA(0:0/18:0),LysoPA(0:0/18:2(9Z,12Z)],LysoPA[20:4(8Z,11Z,14Z,17Z)/0:0)]; phosphatidic acid(PA) [PA(20:3(8Z,11Z,14Z)/0:0),PA(20:4(5Z,8Z,11Z,14Z)/0:0),PA(20:5(5Z,8Z,11Z,14Z,17Z)/0:0)]; lysophosphatidylcholine(LPC) [LPC(18:1),LPC(16:0),LPC[16:1(9Z)/0:0],LPC(17:0),LPC[22:4(7Z,10Z,13Z,16Z),LPC(20:2(11Z,14Z); phosphatidylcholine(PC)(PC(14:0/0:0),PC(16:0/0:0); sphingomyelin(SM) (d18:0/12:0); fatty acid(FA)(18:1(OH3)]. There are 2 kinds of amino acids, including L-glutamate,L-glutamine.There are 3 other metabolites, including retinol,flavin adenine dinucleotide,androsterone glucuronide.Lipid metabolites are the main metabolites in these metabolites.The metabolic pathways related to FTC were analyzed by KEGG and HMDB, and 9 metabolic pathways were found, including 4 amino acid related metabolic pathways, 1 lipid metabolic pathways and 4 other related pathways. Conclusion: There are significant differences in many metabonomic characteristics between FTC and FTN, suggesting that these metabolites can be used as potential biomarkers. Further study found that LysoPA and its analogues can be used as biomarkers in the early diagnosis of FTC.It may be related to the abnormal metabolism of phospholipase D (PLD), the key enzyme of LysoPA synthesis caused by RAS pathway. At the same time, it was found that the metabolic pathway of amino acids and lipids was the main metabolic pathway of FTC. The abnormality of LysoPA may be the cause of follicular tumor carcinogenesis caused by lipid metabolic pathway.

Small RNA expression patterns in seminal plasma exosomes isolated from semen containing spermatozoa with cytoplasmic droplets versus regular exosomes in boar semen.

Multiple physiological pathways are controlled by exosomes. Exosomes may be found in seminal plasma where they carry functional molecules to the sperm, such as microRNAs (miRNAs). Sperm cytoplasmic droplets (CDs) are remnants of cytoplasm, and their migration is a morphological characteristic of epididymal maturation. However, miRNA expression patterns in seminal plasma exosomes found in semen containing spermatozoa with CDs versus regular exosomes in boar semen have not been examined. In this study, seminal plasma exosomes were isolated from semen containing spermatozoa with CDs and miRNA expression profiles were analyzed. A total of 348 known and 206 new miRNAs were identified. Sixteen miRNAs were significantly differentially expressed. Of these, 13 miRNAs (ssc-miR-101, ssc-miR-148a-5p, ssc-miR-184, ssc-miR-202-3p, ssc-miR-221-5p, ssc-miR-2483, ssc-miR-29a-3p, ssc-miR-29c, ssc-miR-31, ssc-miR-362, ssc-miR-500-5p, ssc-miR-542-3p, and ssc-miR-769-5p) were significantly upregulated, whereas three miRNAs (ssc-miR-1249, ssc-miR-155-5p, and ssc-miR-296-5p) were significantly downregulated. GO and KEGG pathway analyses showed that these targeted genes were enriched for functions such as metabolic process, reproductive process, proteasome, ubiquitin mediated proteolysis, and oxidative phosphorylation. Therefore, seminal plasma exosomes are predicted to play a key role in the regulation of sperm CDs.

DNA double-strand break repair gene mutation and the risk of papillary thyroid microcarcinoma: a case-control study.

OBJECTIVE: To study the relationship between DNA double-strand break (DSB) repair gene mutations and the risk of papillary thyroid microcarcinoma (PTMC). METHODS: One hundred patients with PTMC or benign thyroid nodules (BTNs) at Henan Cancer Hospital were retrospectively analyzed. The DSB repair capacity of peripheral blood T lymphocytes in the two groups was assessed by flow cytometry. Data were compared using Student's t-test to evaluate the relationship between DSB repair capacity and the risk of PTMC. Factors influencing DSB repair capacity were analyzed by multivariate logistic regression analysis. The relationship between PTMC and DSB repair capacity was analyzed by univariate analysis. Targeted next-generation DNA sequencing was applied to screen and analyze DSB repair genes related to PTMC. RESULTS: The DSB repair capacity was 31.30% in the PTMC group and 44.40% in the BTN group, with that of the former being significantly lower (P < 0.05). Multivariate logistic regression analysis of age, sex, obesity status, radiation and other factors showed that radiation exposure was positively correlated with reduced DSB repair capacity(OR = 3.642; 95% CI 1.484-8.935, P = 0.020). Moreover, univariate analysis showed that a reduction in DSB repair capacity was a risk factor for PTMC(OR = 2.333; 95% CI 1.027-5.300, P = 0.043).Targeted next-generation DNA sequencing was performed on the DSB repair genes discovered, and those that were mutated in association with PTMC were Rad50 and FANCA; Rad51 mutations were related to BTN. CONCLUSION: Radiation exposure is positively associated with induced DSB repair gene mutations, which may cause a reduced capacity for DSB repair and eventually lead to PTMC.

[Comparison of the diagnostic value of high frequency ultrasound and ultrasound-guided fine needle aspiration biopsy in papillary thyroid microcarcinoma].

Objective:To explore the application value of high frequency ultrasound and ultrasound-guided fine needle aspiration biopsy（US-FNAB） in the diagnosis of papillary thyroid microcarcinoma（PTMC）, and to compare the characteristics and value of the two methods, so as to find a more convenient and non-invasive diagnostic method of PTMC, reduce unnecessary puncture and operation. Methods:The data of 190 postoperative pathologically confirmed PTMC patients admitted to Henan Province Cancer Hospital and Henan Provincial Hospital from January to June 2020 were retrospectively analyzed, with a total of 305 nodules, including 198 PTMC nodules and 107 benign thyroid nodules（BTN）. According to the postoperative pathological results, they were divided into groups, and the relationship between the ultrasound appearance of the nodules and whether the cervical lymph nodes could be explored and PTMC was analyzed by chi-square test and logistic regression, and its diagnostic value was evaluated. The Kappa consistency test was used to analyze the consistency between ultrasound, FNAB and surgical pathological diagnosis results. The accuracy, sensitivity and specificity of high-frequency ultrasound and US-FNAB were compared, and the ROC curve was used to calculate the maximum area under the curve to evaluate its effectiveness. Results:The chi-square test showed that there were statistically significant differences in the morphology, margin, internal echo, echo uniformity, calcification, aspect ratio, blood flow signal, and whether the cervical lymph nodes can be detected and other ultrasound signs between the PTMC group and the BTN group. Logistic regression analysis showed that irregular shape, unclear edges, internal hypoechoic, intranodular calcification are independent risk factors for PTMC. By consistency test, the consistency between high-frequency ultrasound, US-FNAB examination and surgical pathological diagnosis was good, Kappa value was 0.802 and 0.893（P<0.05）. Each nodule was examined by high-frequency ultrasound, and the diagnostic sensitivity, specificity, accuracy and AUC were 95.45%, 83.18%, 91.15% and 0.877 respectively. US-FNAB was performed on 189 of 305 thyroid nodules, and the diagnostic sensitivity, specificity, accuracy and AUC were 96.03%, 93.65%, 95.24% and 0.948 respectively. Conclusion:High frequency ultrasonic features such as internal hypoechoic, calcification in the nodules, unclear edges, and irregular morphology are of high value for the diagnosis of PTMC. Through data analysis, both high-frequency ultrasound and US-FNAB examination have high diagnostic value for PTMC. Compared with US-FNAB, high-frequency ultrasound has the advantages of low examination cost, non-invasive, simple operation and so on. For some patients with PTMC who do not have high risk factors, ultrasound can be used to actively monitor disease progression to avoid some unnecessary surgery.

Intra-arterial versus oscillometric blood pressure measurements in women with severe peripartum hypertension undergoing urgent treatment with nicardipine: An observational study.

OBJECTIVES: The aim of this study was to compare radial arterial catheter-derived pressure with oscillometric blood pressure in women with severe peripartum hypertension undergoing urgent treatment with intravenous nicardipine at a maternal intensive care unit. STUDY DESIGN: We obtained patients' paired values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP). All of the measurements were divided into four groups based on the levels of SBP and MAP measured using the oscillometric method. MAIN OUTCOME MEASURES: We assessed agreements of the paired values using the Bland-Altman method. The clinical relevance of differences between the two methods was assessed by error grid analysis. RESULTS: A total of 337 paired SBP and DBP values and 305 paired MAP values were obtained for 89 patients. The values of intra-arterial SBP were higher than those of oscillometric SBP. The values of intra-arterial MAP were higher than those of oscillometric MAP except for the women with MAP ≥ 125 mm Hg. Bland - Altman analysis showed acceptable agreement for DBP and MAP measured by intra-arterial method and oscillometric method. Error grid analysis showed the proportions of measurements in risk zones A to E were 83.22%, 16.46%, 0.32%, 0%, and 0% for SBP, and 97.81%, 2.19%, 0%, 0%, and 0% for MAP, respectively. CONCLUSION: Intra-arterial MAP can be used reliably to monitor the effect of intravenous nicardipine for treating severe hypertension. Intra-arterial SBP may trigger moderate-risk treatment decisions in the women with oscillometric SBP ≤ 160 mm Hg.

Efficacy of low-dose nicardipine for emergent treatment of severe postpartum hypertension in maternal intensive care units: An observational study.

OBJECTIVES: To investigate the efficacy of low-dose intravenous nicardipine for emergent management of severe postpartum hypertension in maternal intensive care units (ICUs). STUDY DESIGN: The initial dosage of nicardipine was dependent upon patient systolic blood pressure (SBP). Patients with an SBP of 160-179 mmHg received an initial dosage of 2 mg/h, and 4 mg/h was administered to patients where SBP exceeded 180 mmHg. MAIN OUTCOME MEASURES: The efficacy of nicardipine was evaluated by measuring the time interval for achieving the target blood pressure, and its safety was determined by the incidence of severe adverse maternal effects. RESULTS: A total number of 101 patients were admitted to the ICU for severe postpartum hypertension and treated with nicardipine. For patients with an SBP of 160-179 mmHg (n = 28), the interval was 14.04 ± 11.00 min (mean ± SD) for achieving the target blood pressure, and the frequency for adjusting the nicardipine dosage was 1.46 ± 1.17. For patients with an SBP ≥ 180 mmHg (n = 73), the interval was 30.75 ± 16.15 min, and the frequency was 1.62 ± 1.38. Three patients with an SBP ≥ 240 mmHg and/or a diastolic blood pressure (DBP) ≥ 130 mmHg failed to achieve the target blood pressure within 60 min. No severe adverse effects occurred in this study. CONCLUSIONS: Our findings showed that low-dose nicardipine could be used to lower elevated blood pressure safely and rapidly in patients admitted to the ICU for severe postpartum hypertension.

Use of magnetic resonance imaging to assess ovarian maturation in live Rhinogobio ventralis (Sauvage & Dabry de Thiersant, 1874).

The aim of this study is to evaluate the application of magnetic resonance imaging (MRI) to assess ovarian maturation in live female Rhinogobio ventralis (Sauvage & Dabry de Thiersant, 1874). The fish were randomly collected from the Jiangjin area of the Yangtze River between January and April 2014. Magnetic resonance imaging was performed using a 3.0 T clinical MRI scanner with a brain coil and two pulse sequences (IDEAL and 3D CUBE) were employed. Magnetic resonance and histologic images at different stages of ovarian maturation (I-IV) were acquired. An empirical equation (y = -0.1 + 1.56 × x) was derived by traditional method to describe the relationship between the gonadosomatic index (y) and the percentage volume of the ovary (x). A significant correlation (R(2) = 0.977, P < 0.01, N = 53) was found between measurements of the percentage volume of the ovary by MRI and traditional methods. The research findings suggested that MRI was a reliable, rapid, and noninvasive method to assess stages of ovarian maturity in female R. ventralis.