Chemotherapy plus therapeutic plasmapheresis with 4% human albumin solution in multiple myeloma patients with acute kidney injury: a prospective, open-label, proof-of-concept study.

As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median -12.12%, interquartile ranges (IQRs) -18.62 to -5.626) and creatine (median -46.91 µmol/L, IQR -64.70 to -29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03-25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.

Scoparone suppresses mitophagy-mediated NLRP3 inflammasome activation in inflammatory diseases.

Recent evidence shows that targeting NLRP3 inflammasome activation is an important means to treat inflammasome-driven diseases. Scoparone, a natural compound isolated from the Chinese herb Artemisia capillaris Thunb, has anti-inflammatory activity. In this study we investigated the effect of scoparone on NLRP3 inflammasome activation in inflammatory diseases. In LPS-primed, ATP or nigericin-stimulated mouse macrophage J774A.1 cells and bone marrow-derived macrophages (BMDMs), pretreatment with scoparone (50 µM) markedly restrained canonical and noncanonical NLRP3 inflammasome activation, evidenced by suppressed caspase-1 cleavage, GSDMD-mediated pyroptosis, mature IL-1ß secretion and the formation of ASC specks. We then conducted a transcriptome analysis in scoparone-pretreated BMDMs, and found that the differentially expressed genes were significantly enriched in mitochondrial reactive oxygen species (ROS) metabolic process, mitochondrial translation and assembly process, as well as in inflammatory response. We demonstrated in J774A.1 cells and BMDMs that scoparone promoted mitophagy, a well-characterized mechanism to control mitochondrial quality and reduce ROS production and subsequent NLRP3 inflammasome activation. Mitophagy blockade by 3-methyladenine (3-MA, 5 mM) reversed the protective effects of scoparone on mitochondrial damage and inflammation in the murine macrophages. Moreover, administration of scoparone (50 mg/kg) exerted significant preventive effects via inhibition of NLRP3 activation in mouse models of bacterial enteritis and septic shock. Collectively, scoparone displays potent anti-inflammatory effects via blocking NLRP3 inflammasome activation through enhancing mitophagy, highlighting a potential action mechanism in treating inflammasome-related diseases for further clinical investigation.

Capsaicin functions as a selective degrader of STAT3 to enhance host resistance to viral infection.

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Differential metabolism-associated gene expression of duck pancreatic cells in response to two strains of duck hepatitis A virus type 1.

Several outbreaks of duck hepatitis A virus type 1 (DHAV-1), which were characterized by yellow coloration and hemorrhage in pancreatic tissues, have occurred in China. The causative agent is called pancreatitis-associated DHAV-1. The mechanisms involved in pancreatitis-associated DHAV-1 infection are still unclear. Transcriptome analysis of duck pancreas infected with classical-type DHAV-1 and pancreatitis-associated DHAV-1 was carried out. Deep sequencing with Illumina-Solexa resulted in a total of 53.9 Gb of clean data from the cDNA library of the pancreas, and a total of 29,597 unigenes with an average length of 993.43 bp were generated by de novo sequence assembly. The expression levels of D-3-phosphoglycerate dehydrogenase, phosphoserine aminotransferase, and phosphoserine phosphatase, which are involved in glycine, serine, and threonine metabolism pathways, were significantly downregulated in ducks infected with pancreatitis-associated DHAV-1 compared with those infected with classical-type DHAV-1. These findings provide information regarding differences in expression levels of metabolism-associated genes between ducks infected with pancreatitis-associated DHAV-1 and those infected with classical-type DHAV-1, indicating that intensive metabolism disorders may contribute to the different phenotypes of DHAV-1-infection.

Application Value of Real-Time Shear Wave Elastography in Diagnosing the Depth of Infiltrating Muscular Layer of Endometrial Cancer.

OBJECTIVE: To explore the clinical value of real-time shear wave ultrasonic elastography in diagnosing the depth of infiltrating muscularis of endometrial cancer. METHODS: Seventy-one patients with stage I endometrial cancer infiltrating the myometrium and 37 patients with normal physical examination were enrolled and divided into three groups: endometrial cancer superficial muscle infiltration group, endometrial cancer deep muscle infiltration group, and normal control group. After completing 2-dimensional ultrasound examination, each patient switched to the real-time shear wave elastography mode to measure the elasticity values Emax, Emean, and Esd. RESULTS: For control group, comparison of elastic modulus values between superficial muscular layer near the intimal surface and the deep muscular layer near the serosa surface showed no difference (P > 0.05). For endometrial cancer superficial muscular infiltration group, significant difference was found regarding the elastic modulus values of infiltrated muscular layer and uninfiltrated muscular layer (Emax and Emean) without difference for Esd (P > 0.05). A significant difference of elastic modulus was observed between control group and deep myometrial infiltration group (P < 0.05) without difference of Emean or Emax but with difference of Esd. The accuracy in diagnosing muscular layer infiltration was 78.9% for Emax cutoff and 82.5% for Emean cutoff. The rate of using Emax ≥32.22 kPa or Emean ≥27.54 kPa as the ultrasound standard for diagnosing myometrium infiltration was 92.9%. The accuracy for the diagnosis of muscular layer infiltration was 96.1% for Emax cutoff, 94.1% for Emean cutoff and 86.3% for Esd cutoff. CONCLUSION: Real-time shear wave elastography is helpful to determine the depth of infiltrating myometrium of endometrial cancer.

miRNA and circRNA expression patterns in mouse brain during toxoplasmosis development.

BACKGROUND: Increasing evidence has shown that circular RNAs (circRNAs) are involved in neurodegenerative disorders, but their roles in neurological toxoplasmosis are yet to know. This study examined miRNA and circRNA expressions in mouse brain following oral infection with T. gondii Pru strain. RESULTS: Total RNA extracted from acutely infected (11 days post infection (DPI)), chronically infected (35 DPI) and uninfected mouse brain samples were subjected to genome-wide small RNA sequencing. In the acutely infected mice, 9 circRNAs and 20 miRNAs were upregulated, whereas 67 circRNAs and 28 miRNAs were downregulated. In the chronically infected mice, 2 circRNAs and 42 miRNAs were upregulated, whereas 1 circRNA and 29 miRNAs were downregulated. Gene ontology analysis predicted that the host genes that produced the dysregulated circRNAs in the acutely infected brain were primarily involved in response to stimulus and ion binding activities. Furthermore, predictive interaction networks of circRNA-miRNA and miRNA-mRNA were constructed based on genome-wide transcriptome sequencing and computational analyses, which might suggest the putative functions of miRNAs and circRNAs as a large class of post-transcriptional regulators. CONCLUSIONS: These findings will shed light on circRNA-miRNA interactions during the pathogenesis of toxoplasmosis, and they will lay solid foundation for studying the potential regulation roles of miRNAs and circRNAs in T. gondii induced pathogenesis.

Clinical characteristics of a group of deaths with COVID-19 pneumonia in Wuhan, China: a retrospective case series.

BACKGROUND: With the widespread outbreak of novel coronavirus diseases 2019(COVID-19), more and more death cases were reported, however, limited data are available for the patients who died. We aimed to explore the clinical characteristics of deaths with COVID-19 pneumonia. METHODS: We abstracted and analyzed epidemiological, demographic, clinical, and laboratory data from 83 death cases with COVID-19 pneumonia in East Hospital of Wuhan University Renmin Hospital, between January 26, 2020, and February 28, 2020. RESULTS: Of the 83 deaths, none was the medical staff. The mean age was 71.8 years (SD 13.2; range, 34-97 years) and 53(63.9%) were male. The median from onset to admission was 10 days (IQR 7-14: range, 2-43 days), to death was 17 days (IQR 14-21: range, 6-54 days). Most deaths (66[80%]) had underlying comorbid diseases, the most of which was hypertension [47(57%)]. The main initial symptoms of these 83 deaths were shortness of breath(98.8%), fever(94%), and myalgia or fatigue(90.4%). Laboratory analyses showed the lymphocytopenia in 69(83%) deaths, hypoalbuminemia in 77(93%) deaths, the elevation of lactate dehydrogenase in 79(95%) deaths, procalcitonin in 69(83%) deaths and C-reactive protein in 79(95%) deaths. All 83 patients received antiviral treatment, 81(97.6%) deaths received antibiotic therapy, 54(65.1%) deaths received glucocorticoid therapy, and 20(24.1%) patients received invasive mechanical ventilation. CONCLUSION: Most of the deaths with COVID-19 pneumonia were elderly patients with underlying comorbid diseases, especially those over 70 years of age. The time of death after the onset of the disease was mostly 15-21 days. More care should be given to the elderly in further prevention and control strategies of COVID-19.

[Virtual screen of effective AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking].

This research is to predict anti-Alzheimer's disease active constituents on the target of acetylcholinesterase(AChE) from Glycyrrhizae Radix et Rhizoma with the help of pharmacophore and molecular docking. AChE ligand-based pharmacophore model was set up and the molecular library of the constituents from Glycyrrhizae Radix et Rhizoma were established by collecting literature. Then the constituents from Glycyrrhizae Radix et Rhizoma were screen for the potential AChE inhibitory potency in silico through matching with the best pharmacophore model. The flexible docking was used to evaluate the interactions between compounds screened from pharmacophore model and AChE protein(PDB ID:4 EY7). The interactions were expressed including but not limited to CDOCKER interaction energy, hydrogen bonds and non-bonding interactions. The molecular library of Glycyrrhizae Radix et Rhizoma contains 44 chemical constituents. As for the pharmacophore model, six kinds of potential AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma were considered to be the promising compounds according to the results of searching 3 D database of pharmacophore model. The molecular docking was possessed and the interaction patterns were given to show the detail interactions. The compounds screening from the pharmacophore model were consistent with the existing studies to some degree, indicating that the virtual screen protocols of AChE inhibitory constituents from Glycyrrhizae Radix et Rhizoma based on pharmacophore and molecular docking was reliable.

Elevated plasma D-dimer levels are associated with short-term poor outcome in patients with acute ischemic stroke: a prospective, observational study.

BACKGROUND: Elevated levels of plasma D-dimer increase the risk of ischemic stroke, stroke severity, and the progression of stroke status, but the association between plasma D-dimer level and functional outcome is unclear. The aim of this study is to investigate whether plasma D-dimer level is a determinant of short-term poor functional outcome in patients with acute ischemic stroke (AIS). METHODS: This prospective study included 877 Chinese patients with AIS admitted to Renmin Hospital of Wuhan University within 72 h of symptom onset. Patients were categorized by plasma D-dimer level: Quartile 1(≤0.24 mg/L), Quartile 2 (0.25-0.56 mg/L), Quartile 3 (0.57-1.78 mg/L), and Quartile 4 (> 1.78 mg/L). The medical record of each patient was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale. RESULTS: Poor outcome was present in 302 (34.4%) of the 877 patients that were included in the study (mean age, 64 years; male, 68.5%). After adjustment for potential confounding variables, higher plasma D-dimer level on admission was associated with poor outcome (adjusted odds ratio 2.257, 95% confidence interval 1.349-3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor for poor outcome was a plasma D-dimer level ≥ 0.315 mg/L (area under the ROC curve 0.657; sensitivity 83.8%; specificity 41.4%). CONCLUSION: Elevated plasma D-dimer levels on admission are significantly associated with poor outcome after admission for AIS, suggesting the potential role of plasma D-dimer level as a predictive marker for short-term poor outcome in patients with AIS.

Prevalence, genotypes, and risk factors of Enterocytozoon bieneusi in Asiatic black bear (Ursus thibetanus) in Yunnan Province, Southwestern China.

Microsporidiosis is an important zoonotic disease, even leading to severe diarrhea. However, no information about prevalence and genotypes of Enterocytozoon bieneusi infection in Asiatic black bears in southwestern China is available. The objectives of the present study were to investigate the prevalence of E. bieneusi and to characterize their genotypes using the nested PCR amplification of the internal transcribed spacer region of the ribosomal RNA gene cluster and multilocus sequence typing (MLST). The overall prevalence of E. bieneusi was 19.75% (80/405) and the rate of E. bieneusi in Xishuangbanna (33.33%) was significantly higher than that in any other regions (Honghe, 17.65%; Dehong, 13.04%; Kunming, 0; P = 0.01). Sequence analysis revealed that 4 known genotypes (D, n = 2; SC02, n = 10; SC01, n = 5; and CHB1, n = 4) and 13 novel genotypes (designed MJ1-MJ13) were identified. When 17, 5, 14, and 34 sequences at loci MS1, MS3, MS4, and MS7 via MLST analyses, representing 4, 4, 5, and 10 genotypes, respectively, were completed, one multilocus genotype (MLG novel-ABB1) was identified. This is the first report of E. bieneusi in Asiatic black bear in Yunnan province, Southwestern China. The results indicated the potential zoonotic risk of this parasite through the Asiatic black bear in this region and provided foundation data for preventing and controlling E. bieneusi infection of many other animals and humans in these regions.

An Intelligent Computing Method for Contact Plan Design in the Multi-Layer Spatial Node-Based Internet of Things.

Computational Intelligence (CI) has been addressed as a great challenge in recent years, particularly the aspects of routing, task scheduling, and other high-complexity issues. Especially for the Contact Plan Design (CPD) that schedules contacts in dynamic and resource-constrained networks, a suitable CI algorithm can be exchanged for a high-quality Contact Plan (CP) with the appropriate computational overhead. Previous works on CPD mainly focused on the optimization of satellite network connectivity, but most of them ignored network topology characteristics. In this paper, we study the CPD issue in the spatial node based Internet of Things (IoT), which enables the spatial nodes to deliver data cooperatively via intelligent networking. Specifically, we first introduce a Multi-Layer Space Communication Network (MLSCN) model consisting of satellites, High Altitude Platforms (HAPs), Unmanned Aerial Vehicles (UAVs), and ground stations, on which a Time-Evolving Graph (TEG) is used to illustrate the CPD process. Then, according to the characteristics of each layer in the MLSCN, we design the corresponding CPs for the inter-layer contacts and intra-layer contacts. After that, a CI algorithm named as Multidirectional Particle Swarm Optimization (MPSO) is proposed for inter-layer CPD, which utilizes a grid-based initialization strategy to expand the diversity of individuals, in which a quaternary search method and quaternary optimization are introduced to improve efficiency of particle swarms in iterations and to ensure the continuous search ability, respectively. Furthermore, an optimized scheme is implemented for the intra-layer CPD to reduce congestion and improve transmission efficiency. Simulation results show that the proposed CPD scheme can realize massive data transmission with high efficiency in the multi-layer spatial node-based IoT.

Inhibition of AMPK accentuates prolonged caloric restriction-induced change in cardiac contractile function through disruption of compensatory autophagy.

Prolonged caloric restriction often results in alteration in heart geometry and function although the underlying mechanism remains poorly defined. Autophagy, a conserved pathway for bulk degradation of intracellular proteins and organelles, preserves energy and nutrient in the face of caloric insufficiency. This study was designed to examine the role of AMPK in prolonged caloric restriction-induced change in cardiac homeostasis and the underlying mechanism(s) involved with a focus on autophagy. Wild-type (WT) and AMPK kinase dead (KD) mice were caloric restricted (by 40%) for 30 weeks. Echocardiographic, cardiomyocyte contractile and intracellular Ca²âº properties, autophagy and autophagy regulatory proteins were evaluated. Caloric restriction compromised echocardiographic indices (decreased ventricular mass, left ventricular diameters, and cardiac output), cardiomyocyte contractile and intracellular Ca²âº properties associated with upregulated autophagy (Beclin-1, Atg5 and LC3BII-to-LC3BI ratio), increased autophagy adaptor protein p62, elevated phosphorylation of AMPK and TSC1/2, depressed phosphorylation of mTOR and ULK1. Although AMPK inhibition did not affect cardiac mechanical function, autophagy and autophagy signaling proteins, it significantly accentuated caloric restriction-induced changes in myocardial contractile function and intracellular Ca²âº handling. Interestingly, AMPK inhibition reversed caloric restriction-induced changes in autophagy and autophagy signaling. AMPK inhibition led to dampened levels of Beclin-1, Atg 5 and LC3B ratio along with suppressed phosphorylation of AMPK and TSC1/2 as well as elevated phosphorylation of mTOR and ULK1. Taken together, these data suggest an indispensible role for AMPK in the maintenance of cardiac homeostasis under prolonged caloric restriction-induced pathological changes possibly through autophagy regulation. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.

High-power and high-efficiency diode-pumped Nd:LuYAG mixed crystal lasers operating at 939 and 946 nm.

We report on high-performance infrared lasers at 0.94 µm based on quasi-three-level transition of F3/24→I9/24 in Nd:LuYAG mixed crystal, for the first time to our knowledge. The maximum output power was achieved to 5.64 W with slope efficiency of approximately 52.5% at 946 nm. The simultaneous dual-wavelength laser at 939 and 946 nm is also obtained with maximum output power of 3.61 W and slope efficiency of 34.8% by introducing a glass etalon into the cavity. Moreover, a 2.0-W single-wavelength laser at 939 nm can be further attained by suitably tilting the etalon. Using a Cr:YAG saturable absorber, Q-switched laser operation is realized with maximum average output power of 0.68 W and the narrowest pulse width of 8.4 ns, which results in the maximum single pulse energy of approximately 55.3 µJ and the maximum pulse peak power of approximately 6.15 kW. Finally, thermal focal length of the laser crystal is estimated by using a flat-flat laser cavity.

High-Flux Hemodialysis Benefits Hemodialysis Patients by Reducing Serum FGF-23 Levels and Reducing Vascular Calcification.

BACKGROUND: High- and low-flux hemodialysis (HFHD and LFHD, respectively) are dialysis procedures designed to eliminate blood toxins that accumulate in end-stage renal disease. HFHD may reduce vascular calcification by removing serum fibroblast growth factor 23 (FGF-23). However, whether HFHD is better than LFHD is still under debate. We therefore compared the efficacy of HFHD and LFHD in controlling FGF-23 and vascular calcification. MATERIAL AND METHODS: Fifty hemodialysis patients were recruited and randomly treated with either HFHD or LFHD. Fasting venous blood was collected at baseline, six months, and twelve months after the treatment. We then measured levels of FGF-23, calcium, phosphorus, parathyroid hormone, and alkaline phosphatase. Further, abdominal lateral radiographs were taken to calculate aorta abdominalis calcification scores (AACs). RESULTS: Compared to the LFHD group, FGF-23 and AACs in the HFHD group significantly decreased after 12 months treatment (p=0.049 and p=0.002, respectively). AACs were positively correlated with FGF-23 in all patients (p=0.004), the HFHD group alone (p=0.040), and the LFHD group alone (p=0.037). We also found that older patients, patients with higher blood phosphorus levels, and higher FGF-23 levels had an increased risk of aorta abdominalis calcification (p=0.048, p=0.003, p=0.001, respectively). HFHD was more able to reduce the risk of aorta abdominalis calcification than LFHD (p=0.003). CONCLUSIONS: FGF-23 is an independent risk factor for the development of vascular calcification. HFHD may benefit hemodialysis patients by reducing serum FGF-23 levels and controlling vascular calcification.

Water stress enhances expression of genes encoding plastid terminal oxidase and key components of chlororespiration and alternative respiration in soybean seedlings.

Plastid terminal oxidase (PTOX) is a plastid-localized plastoquinone (PQ) oxidase in plants. It functions as the terminal oxidase of chlororespiration, and has the potential ability to regulate the redox state of the PQ pool. Expression of the PTOX gene was up-regulated in soybean seedlings after exposure to water deficit stress for 6 h. Concomitantly expression of the NDH-H gene, encoding a component of the NADPH dehydrogenase (NDH) complex which is a key component of both chlororespiration and NDH-dependent cyclic electron transfer (CET), was also up-regulated. Transcript levels of the proton gradient regulation (PGR5) gene, which encodes an essential component of the PGR5-dependent CET, were not affected by water stress, while the expression of the alternative oxidase (AOX1) gene, which encodes a terminal oxidase of alternative respiration in mitochondria, was also up-regulated under water stress. Therefore, our results indicate that water stress induced the up-regulation of genes encoding key components of chlororespiration and alternative respiration. Transcript levels of the AOX1 gene began to increase in response to water stress before those of PTOX suggesting that alternative respiration may react faster to water stress than chlororespiration.

[SPME-GC-MS combined with Kovat's retention index analysis for volatile components in Pistacia chinensis].

OBJECTIVE: To analyze and compare the volatile components in fruits and leaves of Pistacia chinesis. METHODS: The volatile components were extracted from the fruits and leaves of Pistacia chinesis by solid-phrase microextration, and were analyzed and identified by gas chromatography-mass spectrometry(GC-MS) combined with Kovat's retention index. The relative content of each component was calculated by normalization method. RESULTS: 29 and 17 volatile components were identified from the fruits and leaves respectively, representing the relative content of 95. 30% and 96. 91% of the volatile components. 13 common components were identified in both the fruits and leaves. CONCLUSION: The volatile components in the fruits vary from that in the leaves in type and content, terpenoids are major components in the fruits and leaves of Pistacia chinesis in Shaanxi. Monoterpenes(76. 32%) are the major components of the fruits, while sesquiterpenes(65. 42%) are the major components of the leaves.

Mediation effect of metabolic factors and inflammation on the association of serum uric acid with serum proprotein convertase subtilisin/kexin type 9 levels.

BACKGROUND: The association between serum uric acid (SUA) levels and serum PCSK9 levels has not yet been uncovered. This study aimed to explore the potential link between SUA levels and serum PCSK9 levels and quantify the mediating effect of metabolic factors and inflammation in Chinese adults. Furthermore, assessed whether gender differences modified this association. METHODS: In total, 2624 participants were enrolled and categorized based on their serum UA levels as the hypouricemic (n = 432) and normouricemic group (n = 2192). Stepwise multivariable regression analysis, binary logistic regression analysis and mediation analyses were performed. RESULTS: Participants with hyperuricemia had higher serum PCSK9 levels than those with normouricemia (73.74 ± 30.25 vs 68.55 ± 29.01 ng/ml, P < 0.05), especially in women (69.11 ± 28.84 vs 87.86 ± 27.90 ng/ml, P < 0.001). SUA levels were positively associated with serum PCSK9 levels in all participants (r = 0.06, P < 0.01) and in women (r = 0.22, P < 0.01), but not in men (r = 0.03, P = 0.18). Multiple linear regression and binary logistic regression analyses indicated that serum PCSK9 levels were significantly correlated with SUA levels and hyperuricemia in women. However, when the model was adjusted for triglyceride (TG), the associations of serum PCSK9 levels with SUA levels and hyperuricemia disappeared. In mediation analyses, TG, low-density lipoprotein cholesterol (LDL-C), body mass index(BMI), total cholesterol (TC), white blood cell count and neutrophil count explained 35.08 %, 20.58 %,19.99 %, 14.37 %, 7.10 % and 3.24 % of SUA levels association with serum PCSK9 levels, respectively. CONCLUSION: Serum PCSK9 levels are positively associated with SUA levels in women. Furthermore, this association is partially mediated through metabolic factors and inflammation.

Associated factors of depression in primiparas with hypothyroidism during pregnancy.

This cross-sectional study aimed to explore the associated factors of depression in primiparas with hypothyroidism during pregnancy. The research subjects were 200 primiparas with hypothyroidism during pregnancy who were admitted to our hospital between December 2016 and December 2019. Self-rating depression scale scores were used to evaluate the depression, and the incidence of depression were examined. The data from all the subjects were collected to compare the differences between primiparas with hypothyroidism during pregnancy with and without depression. A logistic regression equation was used to analyze the influencing factors of depression in these patients. Of the 200 primiparas who took part in this study, 27 suffered from depression, accounting for 13.50%. There were differences in age, education level, economic income, sleep quality, and conjugal relations between the depressed and the nondepressed participants. When the above factors were included in the logistic regression equation, it was found that the odds ratio values for these factors were all >1, which indicated that they had an influence on maternal depression in primiparas with hypothyroidism during pregnancy. This study demonstrated that pregnancy-associated hypothyroidism in primiparas is affected by age, education level, economic income, sleep quality, and conjugal relations, all of which increase the incidence of depression. Relevant preventive measures should be provided in clinical practice to avoid the occurrence of depression.

Effect of Internet + continuous midwifery service model on psychological mood and pregnancy outcomes for women with high-risk pregnancies.

BACKGROUND: There are many drawbacks to the traditional midwifery service management model, which can no longer meet the needs of the new era. The Internet + continuous midwifery service management model extends maternal management from prenatal to postpartum, in-hospital to out-of-hospital, and offline to online, thereby improving maternal and infant outcomes. Applying the Internet + continuous midwifery service management model to manage women with high-risk pregnancies (HRP) can improve their psycho-emotional opinion and, in turn, minimize the risk of adverse maternal and/or fetal outcomes. AIM: To explore the effectiveness of a midwife-led Internet + continuous midwifery service model for women with HRP. METHODS: We retrospectively analyzed the clinical data of 439 women with HRP who underwent prenatal examination and delivered at Shanghai Sixth People's Hospital (affiliated to the Shanghai Jiao Tong University School of Medicine) from April to December 2022. Among them, 239 pregnant women underwent routine obstetric management, and 200 pregnant women underwent Internet + continuous midwifery service mode management. We used the State-Trait Anxiety Inventory, Edinburgh Postnatal Depression Scale, and analysis of delivery outcomes to compare psychological mood and the incidence of adverse delivery outcomes between the two groups. RESULTS: The data showed that in early pregnancy, the anxiety and depression levels of the two groups were similar; the levels gradually decreased as pregnancy progressed, and the decrease in the continuous group was more significant [31.00 (29.00, 34.00) vs 34.00 (32.00, 37.00), 8.00 (6.00, 9.00) vs 12.00 (10.00, 13.00), P < 0.05]. The maternal self-efficacy level and strategy for weight gain management were better in the continuous group than in the traditional group, and the effective rate of midwifery service intervention in the continuous group was significantly higher than in the control group [267.50 (242.25, 284.75) vs 256.00 (233.00, 278.00), 74.00 (69.00, 78.00) vs 71.00 (63.00, 78.00), P < 0.05]. The incidence of adverse delivery outcomes in pregnant women and newborns and fear of maternal childbirth were lower in the continuous group than in the traditional group, and nursing satisfaction was higher [10.50% vs 18.83%, 8.50% vs 15.90%, 24.00% vs 42.68%, 89.50% vs 76.15%, P < 0.05]. CONCLUSION: The Internet + continuous midwifery service model promotes innovation through integration and is of great significance for improving and promoting maternal and child health in HRP.

Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway.

The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction (DMED) a challenging endeavor. Notable factors contributing to DMED include oxidative stress, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway activation, and apoptosis, while nitro-oleic acid (NO2-OA) has been shown to be beneficial in treating these aspects of this condition. We, herein, investigated the effects and possible mechanisms of NO2-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes. Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group. However, in response to 4 weeks of NO2-OA treatment, there was an improvement in erectile function. The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group. The expression of proapoptotic factors was increased, while that of antiapoptotic factors was decreased in the DMED group. Moreover, the cell morphology in the cavernous tissue of the DMED group also changed adversely. NO2-OA treatment significantly reversed all these changes observed in the DMED group. In conclusion, NO2-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress, activation of the NO/cGMP pathway, and a reduction in apoptosis.