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1.
J Virol ; 98(2): e0184223, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38179942

ABSTRACT

Macroautophagy/autophagy is a cellular degradation and recycling process that maintains the homeostasis of organisms. A growing number of studies have reported that autophagy participates in infection by a variety of viruses. Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe financial losses to the global swine industry. Although much research has shown that PRRSV triggers autophagy for its own benefits, the exact molecular mechanisms involved in PRRSV-triggered autophagy remain to be fully elucidated. In the current study, we demonstrated that PRRSV infection significantly induced Golgi apparatus (GA) fragmentation, which promoted autophagy to facilitate viral self-replication. Mechanistically, PRRSV nonstructural protein 2 was identified to interact with and degrade the Golgi reassembly and stacking protein 65 dependent on its papain-like cysteine protease 2 activity, resulting in GA fragmentation. Upon GA fragmentation, GA-resident Ras-like protein in brain 2 was disassociated from Golgi matrix protein 130 and subsequently bound to unc-51 like autophagy activating kinase 1 (ULK1), which enhanced phosphorylation of ULK1 and promoted autophagy. Taken together, all these results expand the knowledge of PRRSV-triggered autophagy as well as PRRSV pathogenesis to support novel potential avenues for prevention and control of the virus. More importantly, these results provide the detailed mechanism of GA fragmentation-mediated autophagy, deepening the understanding of autophagic processes.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) infection results in a serious swine disease affecting pig farming worldwide. Despite that numerous studies have shown that PRRSV triggers autophagy for its self-replication, how PRRSV induces autophagy is incompletely understood. Here, we identify that PRRSV Nsp2 degrades GRASP65 to induce GA fragmentation, which dissociates RAB2 from GM130 and activates RAB2-ULK1-mediated autophagy to enhance viral replication. This work expands our understanding of PRRSV-induced autophagy and PRRSV replication, which is beneficial for anti-viral drug development.


Subject(s)
Autophagy , Golgi Apparatus , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Animals , Cell Line , Golgi Apparatus/pathology , Porcine Reproductive and Respiratory Syndrome/pathology , Porcine Reproductive and Respiratory Syndrome/virology , Swine , Virus Replication
2.
Mol Biol Evol ; 40(1)2023 Jan 04.
Article in English | MEDLINE | ID: mdl-36578180

ABSTRACT

Unlike birds and mammals, many teleosts have homomorphic sex chromosomes, and changes in the chromosome carrying the sex-determining locus, termed "turnovers", are common. Recent turnovers allow studies of several interesting questions. One question is whether the new sex-determining regions evolve to become completely non-recombining, and if so, how and why. Another is whether (as predicted) evolutionary changes that benefit one sex accumulate in the newly sex-linked region. To study these questions, we analyzed the genome sequences of two seahorse species of the Syngnathidae, a fish group in which many species evolved a unique structure, the male brood pouch. We find that both seahorse species have XY sex chromosome systems, but their sex chromosome pairs are not homologs, implying that at least one turnover event has occurred. The Y-linked regions occupy 63.9% and 95.1% of the entire sex chromosome of the two species and do not exhibit extensive sequence divergence with their X-linked homologs. We find evidence for occasional recombination between the extant sex chromosomes that may account for their homomorphism. We argue that these Y-linked regions did not evolve by recombination suppression after the turnover, but by the ancestral nature of the low crossover rates in these chromosome regions. With such an ancestral crossover landscape, a turnover can instantly create an extensive Y-linked region. Finally, we test for adaptive evolution of male pouch-related genes after they became Y-linked in the seahorse.


Subject(s)
Smegmamorpha , Animals , Pregnancy , Female , Smegmamorpha/genetics , Evolution, Molecular , Sex Chromosomes/genetics , Genome , Mammals/genetics
3.
BMC Cancer ; 24(1): 756, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38914959

ABSTRACT

BACKGROUND: Anti-vascular endothelial growth factor monoclonal antibody (anti-VEGF) or immune checkpoint inhibitors (ICIs) combined with chemotherapy are commonly administered to cancer patients. Although cancer patients receiving anti-VEGF or ICIs have been reported to experience an increased risk of acute kidney injury (AKI), comparative studies on the AKI incidence have not been evaluated. METHODS: Cancer patients receiving anti-VEGF or ICIs were retrospectively selected from the hospital information system of the First Affiliated Hospital of Wenzhou Medical University between Jan, 2020 and Dec, 2022 and were divided into two groups according to the treatment regimen: anti-VEGF group and ICIs group. The baseline characteristics were propensity-score matched. The primary outcome was sustained AKI. A comparison of cumulative incidence of sustained AKI was performed by Kaplan-Meier curves and log-rank test. Risks for outcomes were assessed using Cox proportional regression. RESULTS: A total of 1581 cancer patients receiving anti-VEGF (n = 696) or ICIs (n = 885) were included in the primary analysis. The ICIs group had a higher cumulative incidence of sustained AKI within one year than the anti-VEGF group (26.8% vs. 17.8%, P < 0.001). Among 1392 propensity score matched patients, ICIs therapy (n = 696) was associated with an increased risk of sustained AKI events in the entire population (HR 2.0; 95%CI 1.3 to 2.5; P = 0.001) and especially in those with genitourinary cancer (HR 4.2; 95%CI 1.3 to 13.2; P = 0.015). Baseline serum albumin level (> 35 g/l) was an important risk factor for a lower incidence of sustained AKI in the anti-VEGF group (HR 0.5; 95%CI 0.3 to 0.9; P = 0.027) and the ICIs group (HR 0.3; 95%CI 0.2 to 0.5; P < 0.001). CONCLUSIONS: Among cancer patients in this real-world study, treatment with ICIs increased incidence of sustained AKI in one year. Baseline serum albumin level was an important risk factor for sustained AKI. The risk factors for sustained AKI differed between the anti-VEGF group and the ICIs group. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov (NCT06119347) on 11/06/2023.


Subject(s)
Acute Kidney Injury , Immune Checkpoint Inhibitors , Neoplasms , Vascular Endothelial Growth Factor A , Humans , Male , Female , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Retrospective Studies , Neoplasms/drug therapy , Neoplasms/complications , Middle Aged , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Incidence , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/administration & dosage
4.
Inorg Chem ; 63(10): 4604-4613, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38395777

ABSTRACT

Nontoxic, highly sensitive InP quantum dot (QD) fluorescent immunoassay probes are promising biomedical detection modalities due to their unique properties. However, InP-based QDs are prone to surface oxidation, and the stability of InP QD-based probes in biocompatible environments remains a crucial challenge. Although the thick shell can provide some protection during the phase transfer process of hydrophobic QDs, the photoluminescence quantum yield (PLQY) is generally decreased because of the contradiction between lattice stress relaxation and thick shell growth. Herein, we developed thick-shell InP-based core/shell QDs by inserting a ZnSeS alloy layer. The ternary ZnSeS intermediate shell could effectively facilitate lattice stress relaxation and passivate the defect states. The synthesized InP/ZnSe/ZnSeS/ZnS core/alloy shell/shell QDs (CAS-InP QDs) with nanostructure tailoring revealed a larger size, high PLQY (90%), and high optical stability. After amphiphilic polymer encapsulation, the aqueous CAS-InP QDs presented almost constant fluorescence attenuation and stable PL intensity under different temperatures, UV radiation, and pH solutions. The CAS-InP QDs were excellent labels of the fluorescence-linked immunosorbent assay (FLISA) for detecting C-reactive protein (CRP). The biotin-streptavidin (Bio-SA) system was first introduced in the FLISA to further improve the sensitivity, and the CAS-InP QDs-based SA-Bio sandwich FLISA realized the detection of CRP with an impressive limit of detection (LOD) of 0.83 ng/mL. It is believed that the stable and sensitive InP QD fluorescent probes will drive the rapid development of future eco-friendly, cost-effective, and sensitive in vitro diagnostic kits.


Subject(s)
Nanostructures , Quantum Dots , Biotin , Streptavidin , Fluorescent Dyes , Alloys
5.
Fish Shellfish Immunol ; 149: 109591, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38679344

ABSTRACT

Toll-like receptors (TLRs) are one of the extensively studied pattern recognition receptors (PRRs) and play crucial roles in the immune responses of vertebrates and invertebrates. In this study, 14 TLR genes were identified from the genome-wide data of Octopus sinensis. Protein structural domain analysis showed that most TLR proteins had three main structural domains: extracellular leucine-rich repeats (LRR), transmembrane structural domains, and intracellular Toll/IL-1 receptor domain (TIR). The results of subcellular localization prediction showed that the TLRs of O. sinensis were mainly located on the plasma membrane. The results of quantitative real-time PCR (qPCR) showed that the detected TLR genes were differentially expressed in the hemolymph, white bodies, hepatopancreas, gills, gill heart, intestine, kidney, and salivary gland of O. sinensis. Furthermore, the present study investigated the expression changes of O. sinensis TLR genes in hemolymph, white bodies, gills, and hepatopancreas in different phases (6 h, 12 h, 24 h, 48 h) after stimulation with PGN, poly(I: C) and Vibrio parahaemolyticus. The expression of most of the TLR genes was upregulated at different time points after infection with pathogens or stimulation with PAMPs, a few genes were unchanged or even down-regulated, and many of the TLR genes were much higher after V. parahaemolyticus infection than after PGN and poly(I:C) stimulation. The results of this study contribute to a better understanding of the molecular immune mechanisms of O. sinensis TLRs genes in resistance to pathogen stimulation.


Subject(s)
Gene Expression Regulation , Immunity, Innate , Octopodiformes , Toll-Like Receptors , Vibrio parahaemolyticus , Animals , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology , Toll-Like Receptors/chemistry , Vibrio parahaemolyticus/physiology , Octopodiformes/genetics , Octopodiformes/immunology , Immunity, Innate/genetics , Gene Expression Regulation/immunology , Phylogeny , Gene Expression Profiling/veterinary , Poly I-C/pharmacology , Peptidoglycan/pharmacology , Arthropod Proteins/genetics , Arthropod Proteins/immunology , Arthropod Proteins/chemistry , Pathogen-Associated Molecular Pattern Molecules/pharmacology
6.
Phys Chem Chem Phys ; 26(15): 12003-12008, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38576321

ABSTRACT

Single-walled carbon nanotubes (SWCNTs) functionalized with sparse surface chemical groups are promising for a variety of optical applications such as quantum information and bio-imaging. However, the luminescence efficiencies and stability, two key aspects, undoubtedly govern their practical usage. Herein, we assess the surface migration of oxygen and triazine groups on as-modified SWCNT fragments by adopting transition state theory and explore the de-excitation of oxygen-functionalized SWCNT fragments by performing non-adiabatic excited-state dynamics simulations. According to the predicted moderate or even small reaction barriers, the migration of both oxygen and triazine groups is feasible from an sp3 defect configuration forming an energetically more stable sp2 configuration at moderate or even room temperatures. Such isomerization leads to drastically different light emission capabilities as indicated by the large or zero oscillator strengths. During the dynamics simulations, the lowest excited singlet (S1) state rapidly decays in energy within 20 fs and then fluctuates until the end, providing insights into the emission mechanism of SWCNTs. This study highlights the potential intrinsic limitations of surface-functionalized SWCNTs for luminescence applications.

7.
J Biopharm Stat ; : 1-20, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639571

ABSTRACT

There are many Bayesian design methods allowing for the incorporation of historical data for sample size determination (SSD) in situations where the outcome in the historical data is the same as the outcome of a new study. However, there is a dearth of methods supporting the incorporation of data from a previously completed clinical trial that investigated the same or similar treatment as the new trial but had a primary outcome that is different. We propose a simulation-based Bayesian SSD framework using the partial-borrowing scale transformed power prior (straPP). The partial-borrowing straPP is developed by applying a novel scale transformation to a traditional power prior on the parameters from the historical data model to make the information better align with the new data model. The scale transformation is based on the assumption that the standardized parameters (i.e., parameters multiplied by the square roots of their respective Fisher information matrices) are equal. To illustrate the method, we present results from simulation studies that use real data from a previously completed clinical trial to design a new clinical trial with a primary time-to-event endpoint.

8.
BMC Public Health ; 24(1): 836, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500120

ABSTRACT

BACKGROUND: Hemodialysis patients require a reasonable dietary intake to manage their disease progression effectively. However, there is limited research on these patients' overall dietary knowledge, attitude, and practice (KAP) status. This study aimed to investigate the dietary KAP status and latent profiles in hemodialysis patients and identify sociodemographic and disease-related factors associated with these profiles and dietary practice. METHODS: A multicenter cross-sectional study involving 425 hemodialysis patients was conducted. A dietary KAP questionnaire in hemodialysis patients was used to evaluate the dietary KAP of the patients. A structural equation model was employed to analyze the correlations between dietary knowledge, attitude, and practice. Multiple linear regression analysis was used to identify factors associated with dietary practice scores. Latent profile analysis was conducted to determine the latent profiles of dietary KAP, and binary logistic regression was used to explore the sociodemographic and disease-related characteristics associated with each KAP profile in hemodialysis patients. RESULTS: The normalized average scores for dietary knowledge, attitude, and practice in hemodialysis patients were 0.58, 0.82, and 0.58, respectively. The structural equation model revealed significant positive correlations between dietary knowledge and attitude, and attitude and practice. Attitude played an indirect effect between knowledge and practice. Gender, cerebrovascular disease, and dietary attitude scores were identified as independent influencing factors for dietary practice scores. Two dietary KAP profiles were developed: a profile with general knowledge and attitude but low practice (40.2%) and a profile with general knowledge and attitude and high practice (59.8%). Binary logistic regression analysis indicated gender and monthly income per household significantly predicted membership in each KAP profile. CONCLUSIONS: The dietary practice of hemodialysis patients requires improvement. It is necessary to develop more individualized dietary interventions for these patients. Further exploration is needed to understand the motivation of patients to change their dietary behavior.


Subject(s)
Diet , Nutritional Status , Humans , Cross-Sectional Studies , Income , Family Characteristics , Health Knowledge, Attitudes, Practice
9.
Proc Natl Acad Sci U S A ; 118(32)2021 08 10.
Article in English | MEDLINE | ID: mdl-34349020

ABSTRACT

Family with sequence similarity 20C (Fam20C), the major protein kinase in the secretory pathway, generates the vast majority of the secreted phosphoproteome. However, the regulatory mechanisms of Fam20C transport, secretion, and function remain largely unexplored. Here, we show that Fam20C exists as a type II transmembrane protein within the secretory compartments, with its N-terminal signal peptide-like region serving as a membrane anchor for Golgi retention. The secretion and kinase activity of Fam20C are governed by site-1 protease (S1P), a key regulator of cholesterol homeostasis. We find that only mature Fam20C processed by S1P functions in osteoblast differentiation and mineralization. Together, our findings reveal a unique mechanism for Fam20C secretion and activation via proteolytic regulation, providing a molecular link between biomineralization and lipid metabolism.


Subject(s)
Casein Kinase I/metabolism , Extracellular Matrix Proteins/metabolism , Proprotein Convertases/metabolism , Serine Endopeptidases/metabolism , Amino Acid Motifs , Animals , COP-Coated Vesicles/metabolism , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Casein Kinase I/genetics , Cell Differentiation/drug effects , Extracellular Matrix Proteins/genetics , Golgi Apparatus/metabolism , HeLa Cells , Humans , Mice , Mutation , Osteoblasts/cytology , Osteoblasts/metabolism , Proprotein Convertases/antagonists & inhibitors , Proprotein Convertases/genetics , Protein Domains , Protein Transport , Pyrrolidines/pharmacology , Secretory Pathway , Serine Endopeptidases/genetics
10.
Arch Gynecol Obstet ; 309(5): 1847-1861, 2024 May.
Article in English | MEDLINE | ID: mdl-38493418

ABSTRACT

PURPOSE: Recurrence of adhesions after hysteroscopic adhesiolysis is a challenging clinical problem without a unified management approach. Therefore, we conducted a network meta-analysis that considered both direct and indirect comparisons between interventions to identify optimal strategies for preventing recurrence. METHODS: We searched for research trials published up to July 2023 from PubMed, Embase and the Cochrane Database. We selected randomized controlled trials comparing the use of different interventions for the prevention of adhesion recurrence, with no language or regional restrictions. We used random-effects models to assess odds ratios (OR) and mean difference (MD) with 95% confidence intervals (CI). Adverse events associated with the interventions were also assessed. This study was registered on PROSPERO, CRD42023449068. RESULTS: Data from 21 randomized controlled trials involving 2406 patients were synthesized, including interventions with balloon, amnion, platelet-rich plasma (PRP), intrauterine device (IUD), hyaluronic acid (HA), platelet-rich fibrin (PRF), and granulocyte colony-stimulating factor (G-CSF). The top 5 interventions for change in AFS scores were: PRP + Balloon (MD = 5.44; 95% CI, 2.63-8.25), Amnion + Balloon (MD = 5.08; 95% CI, 2.71-7.44), IUD + Balloon (MD = 4.89; 95% CI, 2.49-7.30), HA + Balloon (MD = 3.80; 95% CI, 1.78-5.82), and G-CSF + Balloon (MD = 3.84; 95% CI, 1.05-6.63). There were no statistically significant differences between interventions in the recurrence rate of moderate-to-severe uterine adhesions and the clinical pregnancy rate. Most interventions were safe. CONCLUSIONS: To our knowledge, this is the most comprehensive network meta-analysis to date of interventions for preventing postoperative intrauterine adhesion recurrence. Our results indicate that PRP + Balloon seems to be the most effective approach.


Subject(s)
Hysteroscopy , Uterine Diseases , Pregnancy , Female , Humans , Hysteroscopy/adverse effects , Network Meta-Analysis , Randomized Controlled Trials as Topic , Uterine Diseases/surgery , Hyaluronic Acid/therapeutic use , Tissue Adhesions/prevention & control , Tissue Adhesions/surgery , Tissue Adhesions/etiology , Granulocyte Colony-Stimulating Factor
11.
Ren Fail ; 46(2): 2363589, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38874093

ABSTRACT

PURPOSE: To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators. METHODS: This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy. RESULTS: A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients' protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = -2.880, p = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = -0.109, p = 0.001). Pearson correlation analysis revealed that dietary DPI (r = -0.109, p < 0.05), DEI (r = -0.226, p < 0.05) and phosphorus (r = -0.195, p < 0.001) intake were statistically correlated to Kt/V; dietary nDPI (r = 0.101, p < 0.05) and sodium (r = -0.144, p < 0.001) intake were statistically correlated to serum urea nitrogen; dietary DPI (r = 0.200, p < 0.001), DEI (r = 0.241, p < 0.001), potassium (r = 0.129, p < 0.05), phosphorus (r = 0.199, p < 0.001), and fiber (r = 0.157, p < 0.001) intake were statistically correlated to serum creatinine; dietary phosphorus (r = 0.117, p < 0.05) and fiber (r = 0.142, p < 0.001) intake were statistically correlated to serum phosphorus; dietary nDPI (r = 0.125, p < 0.05), DPI (r = 0.135, p < 0.05), nDEI (r = 0.116, p < 0.05), DEI (r = 0.125, p < 0.05), potassium (r = 0.148, p < 0.001), and phosphorus (r = 0.156, p < 0.001) intake were statistically correlated to subjective global assessment scores; dietary nDPI (r = 0.215, p < 0.001), DPI (r = 0.341, p < 0.001), nDEI (r = 0.142, p < 0.05), DEI (r = 0.241, p < 0.001), potassium (r = 0.166, p < 0.05), phosphorus (r = 0.258, p < 0.001), and fiber (r = 0.252, p < 0.001) intake were statistically correlated to handgrip strength in males; dietary fiber (r = 0.190, p < 0.05) intake was statistically correlated to handgrip strength in females. CONCLUSIONS: The dietary nutrient intake of MHD patients need improvement. Inadequate dietary nutrient intake among MHD patients could have a detrimental effect on their blood test indexes and overall nutritional status. It is crucial to address and optimize the dietary intake of nutrients in this patient population to enhance their health outcomes and well-being.


Subject(s)
Energy Intake , Nutritional Status , Renal Dialysis , Humans , Cross-Sectional Studies , Male , Female , Middle Aged , Aged , Dietary Proteins/administration & dosage , Adult , Linear Models , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/physiopathology , Hand Strength , Diet Records , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/diet therapy , Renal Insufficiency, Chronic/physiopathology
12.
J Craniofac Surg ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722565

ABSTRACT

BACKGROUND: Standardized and reliable medical photographs are crucial for preoperative and postoperative comparisons and academic communication in the medical field. There is limited research on photographic techniques in patients with cleft lip. Deformities of the lip and nose in patients with cleft lip are not only associated with morphological abnormalities but also with abnormalities of muscle function. METHODS: Considering the morphology and function of the lips and nose in cleft lip patients, the study captured the deformity of cleft lip patients in 6 positions: frontal view, 45 degrees left-right tilted side view, 90 degrees left-right tilted side view, and basal view, and in 5 facial expressions: tightly closed lips, slightly open mouth, smiling, teeth bared, and pout. RESULTS: In 6 different positions and 5 different expressions, we took pictures of lip and nasal deformities covering most of the common deformities in patients with cleft lip, such as white lip scarring, interruption of continuity of vermillion border, lip prolapse, asymmetric corners of the mouth, collapsed ala nasi, loss of the nasal base and deviated nasal septum. CONCLUSIONS: This paper suggests a set of effective, easy-to-follow, and precise photographic protocols to assist cleft lip surgeons in capturing suitable and informative, high-quality 2D digital photographs. LEVEL OF EVIDENCE: Level-V.

13.
Asia Pac J Clin Nutr ; 33(1): 23-32, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38494684

ABSTRACT

BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Female , Humans , Antineoplastic Agents/adverse effects , Bacteroides fragilis , Breast Neoplasms/drug therapy , Cyclophosphamide/adverse effects , Epirubicin/adverse effects , Granulocyte Colony-Stimulating Factor/therapeutic use , Recombinant Proteins/therapeutic use
14.
J Clin Ultrasound ; 52(5): 535-541, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38485265

ABSTRACT

PURPOSE: This study was designed to investigate the application value of the atrial septum excursion index (ASEI) in fetuses with isolated restrictive foramen ovale (RFO) or redundant foramen ovale flap (RFOF) and the outcomes of these fetuses. METHODS: This was a retrospective study. Healthy pregnant women who were examined by antenatal fetal echocardiography from January 1, 2019 to December 31, 2021, at Sir Run Run Shaw Hospital were enrolled. One hundred seventy-seven (177) fetuses were categorized into three groups by diagnosis: (1) RFOF (n = 33), (2) RFO (n = 21), and (3) normal (n = 123). Fetal echocardiographic features and postnatal outcomes were collected. RESULTS: The median ASEIs were 0.50 (range, 0.41-0.65) in the control group, 0.76 (range, 0.67-0.88) in the RFOF group and 0.31 (range, 0.14-0.35) in the RFO group, and the differences were significant (p < 0.001). The ratios of right atrium/left atrium, right ventricle/left ventricle, and pulmonary artery diameter to aorta diameter (PA/AO) and the pulmonary annulus Z-scores were greater in fetuses with RFOF and RFO than in the controls (p < 0.05). Twenty-seven of 33 fetuses (87.9%) with RFOF and 19 of 21 fetuses (90.5%) with RFO had good outcomes after birth. CONCLUSION: The ASEI may be a new tool for quantitatively assessing the mobility of foramen ovale flaps in fetuses with isolated RFOF or RFO.


Subject(s)
Echocardiography , Foramen Ovale , Ultrasonography, Prenatal , Humans , Female , Pregnancy , Retrospective Studies , Ultrasonography, Prenatal/methods , Adult , Echocardiography/methods , Foramen Ovale/diagnostic imaging , Foramen Ovale/embryology , Foramen Ovale/surgery , Heart Septal Defects, Atrial/surgery , Heart Septal Defects, Atrial/diagnostic imaging , Heart Septal Defects, Atrial/embryology , Fetal Heart/diagnostic imaging , Fetal Heart/physiopathology , Atrial Septum/diagnostic imaging , Atrial Septum/embryology , Atrial Septum/surgery
15.
J Pediatr Nurs ; 78: 14-20, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38843701

ABSTRACT

PURPOSE: This study aimed to explore the real experiences and needs of neonatal intensive care unit (NICU) preterm intergenerational caregivers for discharge preparation and provide a basis for nursing staff to formulate systemic and personalized health education plans and continuous nursing plans for preterm discharge. DESIGN AND METHODS: This was a descriptive qualitative study. An objective sampling method was used to select 16 intergenerational caregivers of preterm infants admitted to the NICU of tertiary obstetrics and gynecology hospitals in Zhejiang and Jilin provinces from December 2023 to February 2024. Semi-structured interviews were conducted on the day of discharge of the preterm infants and six weeks after discharge. Colaizzi's seven-step analysis method was used to analyze the interview data. RESULTS: Based on the existence, relatedness, and growth (ERG) theory, the discharge preparation experiences and needs of neonatal intergenerational caregivers in the NICU were summarized into three themes: psychological condition, care capacity condition, and multi-party support needs. CONCLUSIONS: In the process of hospital discharge preparation, intergenerational caregivers of premature infants in NICU have multiple needs, including enhancing nursing ability and obtaining psychological and multi-party support. It is helpful to take effective interventions to improve their readiness for discharge. PRACTICE IMPLICATIONS: The nursing staff should develop personalized discharge health education plans and continuous nursing plans to improve the level of discharge preparation. PATIENT OR PUBLIC CONTRIBUTIONS: There were no patient or public contributions.

16.
J Tissue Viability ; 33(2): 185-189, 2024 May.
Article in English | MEDLINE | ID: mdl-38521680

ABSTRACT

BACKGROUND: Pediatric burn patients are an essential part of burn populations. However, there is limited publicly available data on the epidemiological impact of COVID-19 on pediatric burns in China. OBJECTIVE: In this paper, pediatric burn patients admitted to the Department of Burn Surgery of the First Hospital of Jilin University before and during COVID-19 were retrospectively investigated to determine the impact of COVID-19 on pediatric burn inpatients. METHODS: The information of inpatients from July 2017 to December 2019 (pre-COVID-19 group) and from January 2020 to June 2022 (COVID-19 group) in the Department of Burn Surgery at the First Hospital of Jilin University was retrospectively investigated. Demographic information of patients, length of hospital stay, total body surface area (TBSA) of burn injury, post-injury visit time, comorbidity, surgical methods, etc., were statistically analyzed. RESULTS: The COVID-19 group included 154 (10.2%) patients, and the pre-COVID-19 group included 335 (19.4%) patients (P<0.001). There were no differences in gender, age, length of hospital stay, or etiology of burns between the two groups. Compared to the pre-COVID-19 group, patients in the pre-COVID-19 group experienced a significant delay in presentation (P<0.001), had a larger TBSA of burn wound (P < 0.001), were more prone to sustaining major burns (P < 0.001), a higher likelihood of undergoing operations (P = 0.03), higher cost (P<0.001) and more complications (P<0.001). Additionally, upper extremities were the most commonly part involved in both groups (P = 0.004), with the lower extremities showed a significant increase to be involved in burn injury during COVID-19 pandemic (P = 0.007). Furthermore, the majority of guardians did not take first aid measures in both groups following burn injury (P = 0.102). CONCLUSIONS: During the COVID-19 pandemic period, scalds remained the main reason for hospitalization. The number of hospitalized patients has decreased dramatically, while the severity of burns has significantly increased, with a notable delay in hospital visits and an increased occurrence of complications.


Subject(s)
Burn Units , Burns , COVID-19 , Humans , COVID-19/epidemiology , Retrospective Studies , Burns/epidemiology , Burns/therapy , China/epidemiology , Male , Female , Child , Burn Units/statistics & numerical data , Burn Units/organization & administration , Child, Preschool , Length of Stay/statistics & numerical data , Adolescent , Infant , Pandemics , SARS-CoV-2
17.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2393-2401, 2024 May.
Article in Zh | MEDLINE | ID: mdl-38812140

ABSTRACT

Rhei Radix et Rhizoma is common traditional Chinese medicine with multiple original plants. The content and proportion of the active components in Rhei Radix et Rhizoma from different plant species were compared to accurately evaluate the medicine qua-lity and provide a theoretical basis for precise use of this medicine in clinical practice. In this study, fresh Rhei Radix et Rhizoma samples were collected from the four-year-old plants of Rheum palmatum, R. tanguticum, and R. officinale. The relative content of 220 anthraquinones, anthrones, and tannins in the samples were determined by pseudo-targeted metabolomics, and the differential components were screened by multivariate statistical methods. The principal component analysis classified the samples into three clusters according to the original plants. The orthogonal partial least squares-discriminant analysis(OPLS-DA) screened out 117 differential components, including 8 free anthraquinones, 18 anthraquinone glycosides, 80 anthrones, and 11 tannins. Twenty-eight components had the highest content in R. tanguticum, mainly including sennosides, anthraquinone glycosides, and procyanidins. Thirty-five components showed the highest content in R. officinale, mainly including free anthraquinones and catechines. Fifty-four components showed the highest content in R. palmatum, mainly including dianthrones, while the structures of most of them cannot be determined temporarily. The content distribution of differential components in the three original plants indicates that R. tanguticum has the strongest effect of purging, while R. officinale has the strongest effect of clearing heat and purging fire, and both have stronger effects of resolvong stasis and dredging meridians than R. palmatum.


Subject(s)
Drugs, Chinese Herbal , Metabolomics , Rheum , Rhizome , Rheum/chemistry , Rhizome/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Anthraquinones/chemistry , Anthraquinones/analysis , Chromatography, High Pressure Liquid
18.
J Virol ; 96(6): e0000522, 2022 03 23.
Article in English | MEDLINE | ID: mdl-35080428

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) has caused huge economic losses to global swine industry. As an intracellular obligate pathogen, PRRSV exploits host cellular machinery to establish infection. The endocytic sorting complex required for transport (ESCRT) system has been shown to participate in different life cycle stages of multiple viruses. In the present study, a systematic small interference RNA screening assay identified that certain ESCRT components contributed to PRRSV infection. Among them, tumor susceptibility gene 101 (TSG101) was demonstrated to be important for PRRSV infection by knockdown and overexpression assays. TSG101 was further revealed to be involved in virion formation rather than viral attachment, internalization, RNA replication and nucleocapsid (N) protein translation within the first round of PRRSV life cycle. In detail, TSG101 was determined to specially interact with PRRSV N protein and take effect on its subcellular localization along with the early secretory pathway. Taken together, these results provide evidence that TSG101 is a proviral cellular factor for PRRSV assembly, which will be a promising target to interfere with the viral infection. IMPORTANCE PRRSV infection results in a serious swine disease affecting pig farming in the world. However, efficient prevention and control of PRRSV is hindered by its complicated infection process. Until now, our understanding of PRRSV assembly during infection is especially limited. Here, we identified that TSG101, an ESCRT-I subunit, facilitated virion formation of PRRSV via interaction with the viral N protein along with the early secretory pathway. Our work actually expands the knowledge of PRRSV infection and provides a novel therapeutic target for prevention and control of the virus.


Subject(s)
DNA-Binding Proteins , Endosomal Sorting Complexes Required for Transport , Nucleocapsid , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Secretory Pathway , Transcription Factors , Animals , Cell Line , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Endosomal Sorting Complexes Required for Transport/genetics , Endosomal Sorting Complexes Required for Transport/metabolism , Nucleocapsid/metabolism , Porcine respiratory and reproductive syndrome virus/genetics , Porcine respiratory and reproductive syndrome virus/metabolism , RNA/metabolism , Secretory Pathway/physiology , Swine , Transcription Factors/genetics , Transcription Factors/metabolism , Virion/metabolism , Virus Replication
19.
J Virol ; 96(4): e0146421, 2022 02 23.
Article in English | MEDLINE | ID: mdl-34586860

ABSTRACT

Bats are reservoirs of important zoonotic viruses like Nipah and SARS viruses. However, whether the blood-sucking arthropods on the body surface of bats also carry these viruses and the relationship between viruses carried by the blood-sucking arthropods and viruses carried by bats have not been reported. This study collected 686 blood-sucking arthropods on the body surface of bats from Yunnan Province, China, between 2012 and 2015, and they included wingless bat flies, bat flies, ticks, mites, and fleas. The viruses carried by these arthropods were analyzed using a meta-transcriptomic approach, and 144 highly diverse positive-sense single-stranded RNA, negative-sense single-stranded RNA, and double-stranded RNA viruses were found, of which 138 were potentially new viruses. These viruses were classified into 14 different virus families or orders, including Bunyavirales, Mononegavirales, Reoviridae, and Picornavirales. Further analyses found that Bunyavirales were the most abundant virus group (84% of total virus RNA) in ticks, whereas narnaviruses were the most abundant (52 to 92%) in the bat flies and wingless bat flies libraries, followed by solemoviruses (1 to 29%) and reoviruses (0 to 43%). These viruses were highly structured based on the arthropod types. It is worth noting that no bat-borne zoonotic viruses were found in the virome of bat-infesting arthropod, seemingly not supporting that bat surface arthropods are vectors of zoonotic viruses carried by bats. IMPORTANCE Bats are reservoirs of many important viral pathogens. To evaluate whether bat-parasitic blood-sucking arthropods participate in the circulation of these important viruses, it is necessary to conduct unbiased virome studies on these arthropods. We evaluated five types of blood-sucking parasitic arthropods on the surface of bats in Yunnan, China, and identified a variety of viruses, some of which had high prevalence and abundance levels, although there is limited overlap in virome between distant arthropods. While most of the virome discovered here is potentially arthropod-specific viruses, we identified three possible arboviruses, including one orthobunyavirus and two vesiculoviruses (family Rhabdoviridae), suggesting bat-parasitic arthropods carry viruses with risk of spillage, which warrants further study.


Subject(s)
Arthropods/virology , Chiroptera/parasitology , Disease Reservoirs/virology , Virome , Animals , Arboviruses/classification , Arboviruses/genetics , Arboviruses/isolation & purification , Arthropods/classification , Arthropods/genetics , China , Disease Reservoirs/parasitology , Ectoparasitic Infestations/parasitology , Ectoparasitic Infestations/veterinary , Ectoparasitic Infestations/virology , Phylogeny , RNA Viruses/classification , RNA Viruses/genetics , RNA Viruses/isolation & purification , Virome/genetics
20.
Stat Med ; 42(1): 1-14, 2023 01 15.
Article in English | MEDLINE | ID: mdl-36318875

ABSTRACT

We develop the scale transformed power prior for settings where historical and current data involve different data types, such as binary and continuous data. This situation arises often in clinical trials, for example, when historical data involve binary responses and the current data involve some other type of continuous or discrete outcome. The power prior, proposed by Ibrahim and Chen, does not address the issue of different data types. Herein, we develop a new type of power prior, which we call the scale transformed power prior (straPP). The straPP is constructed by transforming the power prior for the historical data by rescaling the parameter using a function of the Fisher information matrices for the historical and current data models, thereby shifting the scale of the parameter vector from that of the historical to that of the current data. Examples are presented to motivate the need for such a transformation, and simulation studies are presented to illustrate the performance advantages of the straPP over the power prior and other informative and noninformative priors. A real dataset from a clinical trial undertaken to study a novel transitional care model for stroke survivors is used to illustrate the methodology.


Subject(s)
Models, Statistical , Research Design , Humans , Bayes Theorem , Computer Simulation
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