Mapping the risk factors, pathogens, and antibiotic of pharyngocutaneous fistula in patients after neck open surgery.

PURPOSE: Current literature lacks consensus on risk factors for pharyngocutaneous fistula (PCF), and empirical antibiotic guidelines for PCF are limited. The aim of this study was to reduce the incidence of PCF and improve antibiotic treatment efficacy for patients with PCF after open neck surgery by analyzing their clinical characteristics, pathogenic bacteria, and antibiotic susceptibility. METHODS: This study was a 13-year single-center retrospective cohort study, including 699 patients who underwent open neck surgery for laryngeal and hypopharyngeal cancer. Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with the occurrence of PCF after surgery. The microbial species causing PCF were analyzed, and the antibiotic sensitivity of the top three pathogens was assessed. Venn diagrams were used to illustrate the antibiotics that exhibited 100% sensitivity against all three identified pathogens. RESULTS: The incidence of PCF after open neck surgery was 8%. Logistic univariate and multivariate analyses revealed that flap reconstruction (OR = 3.62, 95% CI [2.02-6.52]), history of preoperative radiotherapy (OR = 2.01, 95% CI [1.31-2.73]), significant postoperative bleeding (OR = 1.79, 95% CI [1.11-2.69]), and history of diabetes (OR = 1.34, 95% CI [1.29-2.46]) were significantly associated with PCF occurrence. Among the 38 cases of PCF patients, the top three identified pathogens were Pseudomonas aeruginosa, Escherichia coli, and Enterobacter cloacae. The antibiotics cefepime, meropenem, ticarcillin/clavulanic acid, and cefoperazone/sulbactam showed 100% sensitivity against these top three pathogens. CONCLUSION: Special attention should be given to patients undergoing open neck surgery, especially those with intraoperative flap reconstruction, a history of preoperative radiotherapy, postoperative bleeding, or diabetes. Strengthening monitoring and care is crucial in preventing the occurrence of PCF. According to antibiotic usage guidelines and considering the distribution of pathogens in PCF patients, empirical antibiotic treatment with cefoperazone/sulbactam or ticarcillin/clavulanic acid is recommended prior to obtaining susceptibility test results.

Composition analysis of Compound Shenhua Tablet, a seven-herb Chinese medicine for IgA nephropathy: evaluation of analyte-capacity of the assays.

Compound Shenhua Tablet, a medicine comprising seven herbs, is employed in treating IgA nephropathy. This study aimed to meticulously analyze its chemical composition. Based on a list of candidate compounds, identified through extensive literature review pertinent to the tablet's herbal components, the composition analysis entailed the systematic identification, characterization, and quantification of the constituents. The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated. The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents' daily doses. A total of 283 constituents, classified into 12 distinct categories, were identified and characterized in the Compound Shenhua Tablet. These constituents exhibited content levels of 1-10 982 µg·g-1, with daily doses of 0.01-395 µmol·d-1. The predominant constituents, with daily doses of ≥ 10 µmol·d-1, include nine organic acids (citric acid, quinic acid, chlorogenic acid, cryptochlorogenic acid, gallic acid, neochlorogenic acid, isochlorogenic acid C, isochlorogenic acid B, and linoleic acid), five iridoids (specnuezhenide, nuezhenoside G13, nuezhenidic acid, secoxyloganin, and secologanoside), two monoterpene glycosides (paeoniflorin and albiflorin), a sesquiterpenoid (curzerenone), a triterpenoid (oleanolic acid), and a phenylethanoid (salidroside). Additionally, there were 83, 126, and 55 constituents detected in the medicine with daily doses of 1-10, 0.1-1, and 0.01-0.1 µmol·d-1, respectively. The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine. This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.

The Born in Guangzhou Cohort Study enables generational genetic discoveries.

Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health1. Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health.

Positive relief of stroke patients with dysphagia under cluster nursing strategy.

For exploring the positive relief effect and application value of cluster nursing strategies on stroke patients with dysphagia in rehabilitation medicine. A retrospective analysis was conducted on 70 patients with stroke dysphagia admitted to the Rehabilitation Medicine Department of our hospital from June 2021 to November 2022; by comparison, patients were separated into intervention group (IG) and control group (CG) according to different degrees of swallowing difficulty, and nutritional nursing interventions were conducted on the selected research subjects. It was given routine care in the CG and a cluster nursing strategy in the IG, with a total intervention time of 5 months. Before intervention, general information of all patients was compared. Before and after intervention, the incidence of aspiration, nutritional biochemical indicators (hemoglobin, total serum protein, albumin, prealbumin, total cholesterol), grip strength, Swallowing Quality of Life score, etc were collected from the 2 groups of patients. Finally, the specific benefits were analyzed through statistical results to evaluate the intervention effect. After intervention, the explicit aspiration rate of the participants in this experiment significantly decreased, and the difference among the participants in this experiment was statistically significant (P < .05); the implicit aspiration rate was not statistically significant (P > .05). In the comparison of nursing expenses, the CG spent 5403.57 ± 815.51 yuan, while the IG spent 5237.10 ± 758.35 yuan. There was a statistically marked disparity among the participants in this experiment (t = 52.41, P < .001). In the comparison of hospitalization expenses, the cost of the CG was 9236.05 ± 3236.08 yuan; The cost of the IG was 9538.59 ± 4985.21 yuan, and there was a marked disparity among the participants in this experiment (P < .001). The significant statistical significance exists (P < .05) in the 5 indicators of hemoglobin, total protein, prealbumin, albumin, and total cholesterol, quality of life scores, and patient physical efficacy in both groups. The intervention study of cluster nursing strategy for stroke patients with dysphagia in rehabilitation medicine can effectively reduce the incidence of overt aspiration and ultimately improve their quality of life. It has high clinical application value.

Ginsenoside Rg3 improves microcystin-induced cardiotoxicity through the miR-128-3p/MDM4 axis.

Microcystin (MC) is the byproduct of cyanobacteria metabolism that is associated with oxidative stress and heart damage. This study aimed to investigate the effect of ginsenoside Rg3 on MC-induced cardiotoxicity. A mouse model of myocardial infarction was constructed by oral MC administration. H9C2 cells were used for in vitro analysis. Cellular oxidative stress, apoptosis, and the relationship between miR-128-3p and double minute 4 protein (MDM4) were analyzed. MiR-128-3p expression was upregulated in vitro and in vivo after MC treatment, which was downregulated after Rg3 treatment. Left ventricular ejection fraction (LVEF) and left ventricular systolic pressure (LVSP) were increased and left ventricular end-diastolic pressure (LVEDP) was decreased after Rg3 treatment. Moreover, Rg3 alleviated MC-induced pathological changes and apoptosis in myocardial tissues. Meanwhile, Rg3 treatment decreased the lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and inhabited cell apoptosis and oxidative stress in MC-treated myocardial cells. MiR-128-3p overexpression attenuated the protective effect of Rg3 on MC-induced cardiotoxicity. MiR-128-3p negatively regulated MDM4 expression. This study revealed that Rg3 alleviated MC-induced cardiotoxicity through the miR-128-3p/MDM4 axis, which emphasized the potential of Rg3 as a therapeutic agent for MC-induced cardiotoxicity, and miR-128-3p as a target for the Rg3 therapy.

Investigating the role of mitochondrial DNA D-loop variants, haplotypes, and copy number in polycystic ovary syndrome: implications for clinical phenotypes in the Chinese population.

Background: The presence of genetic variations in mitochondrial DNA (mtDNA) has been associated with a diverse array of diseases. The objective of this study was to examine the correlations between mtDNA D-loop, its haplotypes, and polycystic ovary syndrome (PCOS) in the Chinese population, and the associations between mtDNA D-loop and symptoms of PCOS. The study also sought to determine whether the mtDNA copy number in Chinese patients with PCOS differed from that of individuals in the control group. Methods: Infertile individuals who only had tubal or male factor treatment were the focus of research by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). mtDNA haplotypes were categorized using polymorphic D-loop sites. mtDNA D-loop, PCOS features, and mtDNA haplotypes were analyzed using R software to determine the strength of the association between the three. There are certain DNA haplotypes linked to PCOS. Microdroplet digital polymerase chain reaction (PCR) was used to determine the mtDNA copy number in a convenience sample of 168 PCOS patients and 83 controls. Results: Among the research group, the majority of D-loop mutations were infrequent (frequency< 1%), with only 45 variants displaying a minimum allele frequency (MAF) of 5% or higher. No association was found between polymorphism loci in PCOS patients and body mass index (BMI). Noteworthy, C194T, 1A200G, 523delAC, and C16234T showed positive correlations with elevated LH/FSH levels. Additionally, specific polymorphic loci G207A, 16036GGins, and 16049Gins within the D-loop region of mtDNA potentially exerted a protective role in PCOS development. Conversely, no statistical significance was observed in the expression levels of C16291T and T489C. Chinese women with mtDNA haplotype A15 exhibited a decreased risk of developing PCOS. Moreover, a significant difference in mtDNA copy number was detected, with controls averaging 25.87 (21.84, 34.81), while PCOS patients had a mean of 129.91 (99.38, 168.63). Conclusion: Certain mtDNA D-loop mutations and haplotypes appear to confer protection against PCOS in Chinese women. In addition, elevated mtDNA copy number may serve as an indicator during early stages of PCOS.

Incremental predictive value of platelet parameters for preeclampsia: results from a large prospective cohort study.

BACKGROUND: Platelet parameters during pregnancy were associated with the risk of preeclampsia (PE), but the predictive value of these parameters for PE remained unclear. Our aim was to clarify the individual and incremental predictive value of platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) for PE. METHODS: This study was based on the Born in Guangzhou Cohort Study in China. Data on platelet parameters were extracted from medical records of routine prenatal examinations. Receiver operating characteristic (ROC) curve was performed to analyze the predictive ability of platelet parameters for PE. Maternal characteristic factors proposed by NICE and ACOG were used to develop the base model. Detection rate (DR), integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI) were calculated compared with the base model to assess the incremental predictive value of platelet parameters. RESULTS: A total of 30,401 pregnancies were included in this study, of which 376 (1.24%) were diagnosed with PE. Higher levels of PC and PCT were observed at 12-19 gestational weeks in women who developed PE later. However, no platelet parameters before 20 weeks of gestation reliably distinguished between PE complicated pregnancy and non-PE complicated pregnancy, with all values of the areas under the ROC curves (AUC) below 0.70. The addition of platelet parameters at 16-19 gestational weeks to the base model increased the DR for preterm PE from 22.9 to 31.4% at a fixed false positive rate of 5%, improved the AUC from 0.775 to 0.849 (p = 0.015), and yielded a NRI of 0.793 (p < 0.001), and an IDI of 0.0069 (p = 0.035). Less but significant improvement in prediction performance was also observed for term PE and total PE when all the four platelet parameters were added to the base model. CONCLUSIONS: Although no single platelet parameter at the early stage of pregnancy identified PE with high accuracy, the addition of platelet parameters to known independent risk factors could improve the prediction of PE.

DHAV 3CD targets IRF7 and RIG-I proteins to block the type I interferon upstream signaling pathway.

Duck hepatitis A virus type 1 (DHAV-1) is an acute, highly lethal infectious agent that infects ducklings and causes up to 95% mortality in ducklings up to 1 week of age, posing a significant economic threat to the duck farming industry. Previous studies have found that the proteolytic enzyme 3 C encoded by DHAV-1 can inhibit the IRF7 protein from blocking the upstream signaling pathway of the type I interferon to promote viral replication. However, there are still few studies on the mechanism of DHAV-1 in immune evasion. Here, we demonstrate that the DHAV-1 3CD protein can interact with IRF7 protein and reduce IRF7 protein expression without directly affecting IRF7 protein nuclear translocation. Further studies showed that the 3CD protein could reduce the expression of RIG-I protein without affecting its transcription level. Furthermore, we found that the 3CD protein interacted with the N-terminal structural domain of RIG-I protein, interfered with the interaction between RIG-I and MAVS, and degraded RIG-I protein through the proteasomal degradation pathway, thereby inhibiting its mediated antiviral innate immunity to promote DHAV-1 replication. These data suggest a novel immune evasion mechanism of DHAV-1 mediated by the 3CD protein, and the results of this experiment are expected to improve the understanding of the biological functions of the viral precursor protein and provide scientific data to elucidate the mechanism of DHAV-1 infection and pathogenesis.

LncRNA XIST promotes carboplatin resistance of ovarian cancer through activating autophagy via targeting miR-506-3p/FOXP1 axis.

OBJECTIVE: Resistance to chemotherapy drugs makes ovarian cancer (OC) difficult to treat and ultimately kills patients. Long non-coding RNAs are closely related to carboplatin resistance in OC. In present study, we explored the role of lncRNA X-inactive specific transcript (XIST) on carboplatin resistance in OC. METHODS: Cell viability, proliferation, and apoptosis were assessed through 2,5-diphenyl-2H-tetrazolium bromide, colony formation, and flow cytometry assays, respectively. Microtubule-associated protein 1A/1B-light chain 3 expression was evaluated by immunofluorescence assay to analyze the cell autophagy. The interaction of XIST/miR-506-3p or miR-506-3p/forkhead box protein P1 (FOXP1) was analyzed using RNA immunoprecipitation (RIP) and dual-luciferases reporter assays. The function of XIST/miR-506-3p/FOXP1 axis in vivo was further confirmed by tumor xenograft study and immunohistochemistry. RESULTS: The expression of XIST and FOXP1 increased while miR-506-3p decreased in OC and carboplatin resistance cells. XIST silencing repressed the proliferative and autophagic capacities of carboplatin resistance cells while promoted the apoptosis. XIST overexpression led to the opposite results. XIST targeted miR-506-3p and downregulated its expression. MiR-506-3p inhibition facilitated the proliferative and autophagic capacities while suppressed the apoptosis of cells, XIST knockdown reversed these effects. MiR-506-3p bound to FOXP1. XIST knockdown or miR-506-3p overexpression reversed the increase of cell proliferative and autophagic abilities and the decrease of apoptosis rate induced by FOXP1 overexpression. XIST affected autophagy and carboplatin resistance in vivo via regulating the miR-506-3p/FOXP1 axis. CONCLUSION: XIST knockdown inhibited autophagy and carboplatin resistance of OC through FOXP1/protein kinase B (AKT)/mammalian target of rapamycin pathway by targeting miR-506-3p.

Preventive Electroacupuncture Alleviates Oxidative Stress and Inflammation via Keap1/Nrf2/HO-1 Pathway in Rats with Cyclophosphamide-Induced Premature Ovarian Insufficiency.

Electroacupuncture (EA) is a popular therapeutic therapy for premature ovarian insufficiency (POI). However, little has been known about the underlying processes of EA therapy. To investigate the benefit of EA and reveal the mechanism, thirty SD female rats were allocated into the control, model, sham, EA, and GnRHa groups at random. Vaginal smears were used to monitor the rats' estrous cycle. Serum liver and renal function (ALT, AST, BUN, and Cr), sex hormone (FSH, E2, and AMH), oxidative stress markers (SOD, GSH, and MDA), and inflammatory cytokine (IL6, IL1ß, and TNFα) levels were measured by enzyme-linked immunosorbent assay (ELISA). Their ovary morphology was observed by hematoxylin-eosin staining. Transmission electron microscope was used to remark the ultrastructure of the granulocytes. Protein and gene expressions of Keap1/Nrf2/HO-1 pathway were detected by western blot and RT-PCR. Compared with the model group, in the EA group, the levels of serum sex hormones recovered to normal levels. Moreover, it reduced oxidative stress in rats, as demonstrated by increased SOD and GSH levels and decreased MDA levels. Meanwhile, Keap1 mRNA and protein expression dropped considerably in the EA group, while the mRNA and protein expressions of Nrf2 and HO-1 increased. We found that preventive EA might rescue rats with CTX-induced ovarian dysfunction. The anti-inflammatory and antioxidative stress properties of EA, which elevated the Keap1/Nrf2/HO-1 signaling pathway, might be the underlying mechanism. Furthermore, as compared to GnRHa, electroacupuncture did not raise the burden of the liver (ALT and AST) or the kidney (BUN and Cr). Electroacupuncture has a meaningful impact and a sufficient level of safety, making it useful for therapeutic setting in POI.

Blood pressure trajectories during pregnancy and preterm delivery: A prospective cohort study in China.

Women's blood pressure (BP) changes throughout pregnancy. The effect of BP trajectories on preterm delivery is not clear. The authors aim to evaluate the association between maternal BP trajectories during pregnancy and preterm delivery. The authors studied pregnant women included in the Born in Guangzhou Cohort Study in China between February 2012 and June 2016. Maternal BP was measured at antenatal visits between 13 and 40 gestational weeks, and gestational age of delivery data was collected. The authors used linear mixed models to capture the BP trajectories of women with term, and spontaneous and iatrogenic preterm delivery. BP trajectories of women with various gestational lengths (34, 35, 36, 37, 38, 39, 40 weeks) were compared. Of the 17 426 women included in the analysis, 618 (3.55%) had spontaneous preterm delivery; 158 (.91%) had iatrogenic preterm delivery; and 16 650 (95.55%) women delivered at term. The BP trajectories were all J-shaped curves for different delivery types. Women with iatrogenic preterm delivery had the highest mean BP from 13 weeks till delivery, followed by those with spontaneous preterm delivery and term delivery (p < .001). Trajectory analysis stratified by maternal parity showed similar results for nulliparous and multiparous women. Excluding women with pre-eclampsia and gestational hypertension (GH) significantly attenuated the aforementioned association. Also, women with shorter gestational length tend to have higher BP trajectories during pregnancy. In conclusion, Women with spontaneous preterm delivery have a higher BP from 13 weeks till delivery than women with term delivery, while women with iatrogenic preterm delivery have the highest BP.

Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.

Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby promoting viral proliferation. Viroporins have multifaceted effects on host cell biological functions, including altering cell membrane permeability, triggering inflammasome formation, inducing apoptosis and autophagy, and evading immune responses, thereby ensuring that the virus completes its life cycle. Viroporins are also virulence factors, and their complete or partial deletion often reduces virion release and reduces viral pathogenicity, highlighting the important role of these proteins in the viral life cycle. Thus, viroporins represent a common drug-protein target for inhibiting drugs and the development of antiviral therapies. This article reviews current studies on the functions of viroporins in the viral life cycle and their regulation of host cell responses, with the aim of improving the understanding of this growing family of viral proteins.

[Expressions of FOXO1/3a/4/6 in human testis and their roles in testicular aging].

OBJECTIVE: To investigate the expression rules of FOXO1a, FOXO3a, FOXO4 and FOXO6 proteins in the human testis, and explore their roles in the development and progression of testicular aging. METHODS: We collected the para-carcinoma testis tissue from 4 testis cancer patients aged 28, 31, 32 and 46 years, and the testis tissue from another 2 PCa patients aged 66 and 81 years after castration surgery from January 2018 to December 2020. We detected the expressions of FOXO1a, FOXO3a, FOXO4 and FOXO6 proteins in the testis tissue by Western blot, determined the locations of FOXO1a, FOXO3a, FOXO4 and FOXO6 in the testis cells by immunofluorescence staining, and performed semi-quantitative and statistical analyses using image J and SPSS 23.0 software, respectively. RESULTS: The expression levels of FOXO1a and FOXO3a proteins were significantly decreased in the testis tissue of the elderly patients (P < 0.01), with an age-dependent reduction in the proportion of the positive cells. No statistically significant difference was observed in the expression levels of FOXO4 and FOXO6 between different age groups. FOXO1a was mainly expressed at the base of the seminiferous tubules, FOXO3a and FOXO4 in the Leydig cells, and FOXO6 in the seminiferous tubules. In addition, FOXO4 underwent age-related nuclear translocation in the senescent Leydig cells, suggesting its involvement in the aging of Leydig cells. CONCLUSION: FOXO1a/3a/4 may be closely related to human testicular aging and corresponding pathological changes, but its underlying mechanism remains to be further explored.

Part 2: Stabilization/Containment of Radiological Particle Contamination to Enhance First Responder, Early Phase Worker, and Public Safety.

The application of stabilization technologies to a radiologically contaminated surface has the potential for reducing the spread of contamination and, as a result, decreasing worker exposure to radiation. Three stabilization technologies, calcium chloride (CaCl2), flame retardant Phos-Chek® MVP-Fx, and Soil2O™ were investigated to evaluate their ability to reduce the resuspension and tracking of radiological contamination during response activities such as vehicle and foot traffic. Concrete pavers, asphalt pavers, and sandy soil walking paths were used as test surfaces, along with simulated fallout material (SFM) tagged with radiostrontium (Sr-85) applied as the contaminant. Radiological activities were measured using gamma spectrometry before and after simulated vehicle operation and foot traffic experiments, conducted with each stabilization technology and without application as a nonstabilized control. These measurements were acquired separately for each combination of surface and vehicle/foot traffic experiment. The resulting data describes the extent of SFM removed from each surface onto the tires or boots, the extent of SFM transferred to adjacent surfaces, and the residual SFM remaining on the tires or boots after each experiment. The type of surface and response worker actions influenced the stabilization results. For instance, when walked over, less than 2% of particles were removed from nonstabilized concrete, 4% from asphalt, and 40% of the particles were removed from the sand surface. By contrast, for vehicle experiments, ~40% of particles were again removed from the sand, but 7% and 15% from concrete and asphalt, respectively. In most cases, the stabilization technologies did provide improved stabilization. The improvement was related to the type of surface, worker actions, and stabilizer; a statistical analysis of these variables is presented. Overall, the results suggest an ability to utilize these technologies during the planning and implementation of response activities involving foot and vehicle traffic. In addition, resuspension of aerosolizable range SFM was monitored during walking path foot traffic experiments, and all stabilizing agents decreased the measured radioactivity, with the Soil2O™ decrease being 3 fold, whereas the CaCl2 and Phos-Chek MVP-Fx surfaces generated no detectable radioactivity. Overall, these results suggest that the stabilization technologies decrease the availability of particles respirable by response workers under these conditions.

Platelet parameters and risk of hypertension disorders of pregnancy: a propensity score adjusted analysis.

While the role of platelets in cardiovascular diseases among the general population has been widely reported, evidence is inconsistent regarding the association between platelet indices with hypertension in pregnant women. In this study, we explored the associations between platelet parameters before 20 gestational weeks, an understudied period, with hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PEEC) and gestational hypertension (GH). Based on the Born in Guangzhou Cohort Study, 12053 singleton pregnant women with platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) measured at 14-19 gestational weeks were included. Conventional multivariable adjustment and propensity score analysis were used to control for confounders. The restricted cubic spline showed that the risk of PEEC increased linearly for PC, and non-linearly for PCT. For GH, the risk increased linearly for PC, MPV, and PCT, and non-linearly for PDW. When these indices were categorized into quintiles, women with higher PC and PCT were associated with increased risk of both PEEC and GH. Women with MPV exceeding the second quintile (≥ 8.8 fL) had a greater risk for GH, but not for PEEC. When HDP was classified into two groups (early- vs late-onset) based on the occurrence time, significant associations persisted for early-onset PEEC, early-onset GH, and late-onset GH. In conclusion, increased PC and PCT before 20 weeks of gestation were both associated with higher risk of PEEC and GH, while elevated MPV was only linked to GH.

Concentration profiles of per- and polyfluoroalkyl substances in major sources to the environment.

A review of published literature was conducted to present the concentrations and composition profiles of per- and polyfluoroalkyl substances (PFAS) from significant sources to the environment. The major sources of PFAS to the environment are categorized under direct and indirect sources. The characteristic compounds and concentrations are summarized as found from direct sources such as manufacturing facilities, aqueous film-forming foam (AFFF) applications, metal coating operations, and textile and paper coating operations; and from indirect sources such as landfills and wastewater treatment plants (WWTPs). The major findings are: 1) among the aqueous matrices for which data were reviewed, groundwater impacted by AFFF contamination showed the highest median concentrations for both perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), while the second-highest median concentrations were associated with landfill leachates for PFOA and metal-plating sources for PFOS; 2) many of the unknown polyfluorinated precursors present in AFFF-impacted sites could potentially convert to persistent PFAS by abiotic or biotic transformation, and therefore could act as the long-term source of contamination to the environment; 3) part per billion (ppb) concentrations of PFAS were detected in water bodies surrounding fluorochemical manufacturing plants; 4) in consumer products such as textile, paper, and personal care products, PFOA concentrations were an order of magnitude higher compared to other PFAS; 5) biotransformation products such as fluorotelomer carboxylic acids (FTCAs) and perfluoroalkyl acids (PFAAs) are detected in landfill leachates and WWTP effluents; and 6) many studies have shown increased PFAA concentrations in WWTP effluents compared to influents. This work provides a comprehensive review of the literature on the PFAS concentration and composition trends of select non-polymeric PFAS in different sources.

Redox sensitive nano-capsules self-assembled from hyaluronic acid-hydroxychloroquine conjugates for CD44-targeted delivery of hydroxychloroquine to combat breast cancer metastasis in vitro and in vivo.

Identifying an efficient tumor-targeted drug delivery system is an urgent task for the treatment of metastatic breast cancer. Herein, we report for the first time that a pH and redox dual-responsive polymer prodrug displays prominent inhibition of breast cancer metastasis to the lung. The polymer molecule was synthesized from hyaluronic acid (HA) and hydroxychloroquine (HCQ) through disulfide bonds as redox-sensitive linkers that self-assemble into nanocapsules (HA-ss-HCQ nanocapsules) at pH 7.4. Due to the pKa value of HCQ and built-in disulfide bonds, the nanocapsules were endowed with pH and redox dual-responsive properties. The in vitro drug release curve revealed that HA-ss-HCQ nanocapsules release drugs more quickly under low pH and high redox conditions. Moreover, the nanocapsules displayed active targeting and selectivity to metastatic breast cancer cells. Cellular uptake of Nile red-loaded nanocapsules observed by fluorescence microscopy showed that the nanocapsules exerted significantly enhanced cellular internalization capacity, which was greatly diminished by free HA. The IC50 of HA-ss-HCQ nanocapsules in 4T1 cells was 2.23-fold lower than that of free HCQ. Importantly, wound healing assays and Transwell experiments demonstrated that HA-ss-HCQ nanocapsules greatly inhibited the migration and invasion of 4T1 cells. In particular, the metastasis of 4T1 cells to the lung was also remarkably suppressed by HA-ss-HCQ nanocapsules with minimal toxicity in an in vitro lung metastasis model, which was verified by the detection of macroscopic metastatic nodules and histological examination. In summary, this study provides a promising strategy for active-targeting therapy in metastatic breast cancer.

Prevalence of High-Risk Human Papillomavirus by Subtypes Among Rural Women Aged 35-64 Years - Guangzhou City, Guangdong Province, China, 2019-2021.

What is already known about this topic?: Little is known about the infection pattern for high-risk human papillomavirus (hrHPV) subtypes in rural areas in southern China. What is added by this report?: The prevalence of HPV-16, 18, and the other 12 hrHPV subtypes were 0.71%, 0.34%, and 4.50%, respectively, among rural women in Guangzhou. The prevalence of HPV-16 and the other 12 hrHPV subtypes increased with age, but there was no evident age trend for HPV-18 prevalence. What are the implications for public health practice?: Epidemiological characteristics of hrHPV prevalence in rural Guangzhou should be considered to identify high-risk populations of hrHPV infection and determine follow-up strategies.

DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein.

Duck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1 contains a viral protein that can regulate the innate immunity of host cells and its specific regulatory mechanism, further exploring the mechanism by which DHAV-1 resists the host immune response. In the study, the dual-luciferase reporter gene system was used to screen the viral protein that regulates the host innate immunity and the target of this viral protein. The results indicate that the DHAV-1 3C protein inhibits the pathway upstream of interferon (IFN)-ß by targeting the interferon regulatory factor 7 (IRF7) protein. In addition, we found that the 3C protein inhibits the nuclear translocation of the IRF7 protein. Further experiments showed that the 3C protein interacts with the IRF7 protein through its N-terminus and that the 3C protein degrades the IRF7 protein in a caspase 3-dependent manner, thereby inhibiting the IFN-ß-mediated antiviral response to promote the replication of DHAV-1. The results of this study are expected to serve as a reference for elucidating the mechanisms of DHAV-1 infection and pathogenicity.