Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution.

BACKGROUND: Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected. METHODS: We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima's D, FST, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes. RESULTS: Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host. CONCLUSIONS: Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.

Deep dewatering of sludge and resource recovery of hydroxyapatite: A recyclable approach via ionic liquid biphasic system and hydrogen bonds reformation.

Deep dewatering of Waste Activated Sludge (WAS) through mechanical processes remains inefficient, primarily due to the formation of a stable hydrogen bonding network between the biopolymers and water, which consequently leads to significant water trapped by Extracellular Polymeric Substances (EPS). In this study, a novel and recyclable treatment for WAS based on Ionic Liquids (ILs) was established, named IL-biphasic aqueous system (IL-ABS) treatment. Specifically, the IL-ABS formed in WAS facilitated rapid and efficient in-situ deep dewatering while concurrently recovering hydroxyapatite. The water content decreased from an initial 98.27 % to 65.35 % with IL-ABS, formed by 1-Butyl-3-methylimidazolium bromide (BmimBr) and K3PO4 synthesized from waste H3PO4. Moreover, the recycled BmimBr maintaining the water content of the dewatered sludge consistently between 65.61 % and 67.25 % across five cycles, exhibited remarkable reproducibility. Through three-dimensional excitation-emission matrix, lactate dehydrogenase analyses and confocal laser scanning microscopy, the high concentration of BmimBr in the upper phase effectively disrupted the cells and EPS, which exposed protein and polysaccharide on the EPS surface. Subsequently, the K3PO4 in the lower phase led to an enhanced salting-out effect in WAS. Furthermore, FT-IR analysis revealed that K3PO4 disrupted the original hydrogen bonds between EPS and water. Then, BmimBr formed numerous hydrogen bonds with the sludge flocs, leading to deep dewatering and agglomeration of the sludge flocs during the unique phase separation process of IL-ABS. Notably, sludge-derived hydroxyapatite product exhibited remarkable adsorption capacity for prevalent heavy metal contaminants such as Pb2+, Cd2+ and Cu2+, with efficiencies comparable to those of commercial hydroxyapatite, thereby achieving the resource utilization of waste H3PO4. Moreover, economic calculations demonstrated the suitability of this novel treatment. This innovative treatment exhibits potential for practical applications in the non-mechanical deep dewatering of WAS.

A superior zinc-air battery performance achieved by CoO/Fe3O4 heterostructured nanosheets.

CoO/Fe3O4 nanosheets exhibit a superior rechargeable zinc-air battery (ZAB) performance of 276 mW cm-2 and stability over 600 h. The all-solid-state ZAB also affords a high power density of 107 mW cm-2.

Portable T-2 toxin biosensor based on target-responsive DNA hydrogel using water column height as readout.

T-2 toxin, a hazardous mycotoxin often present in cereals and products based on cereals, poses a substantial risk to humans and animals due to its high toxicity. The development of uncomplicated, quick and highly sensitive methods for detecting T-2 toxin is imperative. In this work, a portable sensing system was constructed using water column height as a readout device in combination with a controlled release system, which allows for an accurate quantitative analysis of T-2 toxin without the need for expensive instrumentation or skilled technicians. Hyaluronic acid (HA) hydrogel was constructed by double cross-linked DNA/aptamer hybrids with polyethyleneimine (PEI) and embedded with platinum nanoparticles (Pt NPs). The aptamer specifically bound to T-2 toxin in its presence, resulting in the disruption of the hydrogel and subsequent release of the Pt NPs. These Pt NPs were later mixed with a solution of H2O2 in a confined reaction flask, leading to the decomposition of H2O2 into O2. A glass capillary tube containing a column of red water had been inserted into the cap of the reaction flask, and the low solubility of O2 led to an increase in pressure within the reaction unit, causing the red water column to rise. There is a good linear correlation between the height of the capillary liquid level and the T-2 toxin concentration in the range of 20 ng/mL to 6 µg/mL. The system has been successfully used to detect T-2 toxin in samples of barley tea and corn.

HELQ deficiency impairs the induction of primordial germ cell-like cells.

Helicase POLQ-like (HELQ) is a DNA helicase essential for the maintenance of genome stability. A recent study identified two HELQ missense mutations in some cases of infertile men. However, the functions of HELQ in the process of germline specification are not well known and whether its function is conserved between mouse and human remains unclear. Here, we revealed that Helq knockout (Helq-/-) could significantly reduce the efficiency of mouse primordial germ cell-like cell (PGCLC) induction. In addition, Helq-/- embryonic bodies exhibited a severe apoptotic phenotype on day 6 of mouse PGCLC induction. p53 inhibitor treatment could partially rescue the generation of mouse PGCLCs from Helq mutant mouse embryonic stem cells. Finally, the genetic ablation of HELQ could also significantly impede the induction of human PGCLCs. Collectively, our study sheds light on the involvement of HELQ in the induction of both mouse and human PGCLCs, providing new insights into the mechanisms underlying germline differentiation and the genetic studies of human fertility.

The immune cells in modulating osteoclast formation and bone metabolism.

Osteoclasts are pivotal in regulating bone metabolism, with immune cells significantly influencing both physiological and pathological processes by modulating osteoclast functions. This is particularly evident in conditions of inflammatory bone resorption, such as rheumatoid arthritis and periodontitis. This review summarizes and comprehensively analyzes the research progress on the regulation of osteoclast formation by immune cells, aiming to unveil the underlying mechanisms and pathways through which diseases, such as rheumatoid arthritis and periodontitis, impact bone metabolism.

Competitive adsorption of microRNA-532-3p by circular RNA SOD2 activates Thioredoxin Interacting Protein/NLR family pyrin domain containing 3 pathway and promotes pyroptosis of non-alcoholic fatty hepatocytes.

OBJECTIVE: There is a growing body of evidence indicating that pyroptosis, a programmed cell death mechanism, plays a crucial role in the exacerbation of inflammation and fibrosis in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Circular RNAs (circRNAs), functioning as vital regulators within NAFLD, have been shown to mediate the process of cell pyroptosis. This study aims to elucidate the roles and mechanisms of circRNAs in NAFLD. METHODS: Utilizing a high-fat diet (HFD)-induced rat model for in vivo experimentation and hepatocytes treated with palmitic acid (PA) for in vitro models, we identified circular RNA SOD2 (circSOD2) as our circRNA of interest through analysis with the circMine database. The expression levels of associated genes and pyroptosis-related proteins were determined using quantitative real-time polymerase chain reaction and Western blotting, alongside immunohistochemistry. Serum liver function markers, cellular inflammatory cytokines, malondialdehyde, lactate dehydrogenase levels, and mitochondrial membrane potential, were assessed using enzyme-linked immunosorbent assay, standard assay kits, or JC-1 staining. Flow cytometry was employed to detect pyroptotic cells, and lipid deposition in liver tissues was observed via Oil Red O staining. The interactions between miR-532-3p/circSOD2 and miR-532-3p/Thioredoxin Interacting Protein (TXNIP) were validated through dual-luciferase reporter assays and RNA immunoprecipitation experiments. RESULTS: Our findings demonstrate that, in both in vivo and in vitro NAFLD models, there was an upregulation of circSOD2 and TXNIP, alongside a downregulation of miR-532-3p. Mechanistically, miR-532-3p directly bound to the 3'-UTR of TXNIP, thereby mediating inflammation and cell pyroptosis through targeting the TXNIP/NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway. circSOD2 directly interacted with miR-532-3p, relieving the suppression on the TXNIP/NLRP3 signaling pathway. Functionally, the knockdown of circSOD2 or TXNIP improved hepatocyte pyroptosis; the deletion of miR-532-3p reversed the effects of circSOD2 knockdown, and the deletion of TXNIP reversed the effects of circSOD2 overexpression. Furthermore, the knockdown of circSOD2 significantly mitigated the progression of NAFLD in vivo. CONCLUSION: circSOD2 competitively sponges miR-532-3p to activate the TXNIP/NLRP3 inflammasome signaling pathway, promoting pyroptosis in NAFLD.

Ethnic disparities and temporal trends in health resource allocation: a retrospective decadal analysis in Sichuan, a multi-ethnic Province of Southwest China (2009-2019).

BACKGROUND: Research on health resource allocation trends in ethnic minority and impoverished areas in China is limited since the 2009 Medical Reform. This study aimed to investigate the variations and inequalities in health resource distribution among ethnic minority, poverty-stricken, and non-minority regions in Sichuan Province, a multi-ethnic province in Southwest China, from 2009 to 2019. METHODS: The numbers of beds, doctors and nurses were retrospectively sourced from the Sichuan Health Statistics Yearbook between 2009 and 2019. All the 181 counties in Sichuan Province were categorized into five groups: Yi, Zang, other ethnic minority, poverty-stricken, and non-minority county. The Theil index, adjusted for population size, was used to evaluate health resource allocation inequalities. RESULTS: From 2009 to 2019, the number of beds (Bedp1000), doctors (Docp1000), and nurses (Nurp1000) per 1000 individuals in ethnic minority and poverty-stricken counties consistently remained lower than non-minority counties. The growth rates of Bedp1000 in Yi (140%) and other ethnic minority counties (127%) were higher than in non-minority counties (121%), while the growth rates of Docp1000 in Yi (20%) and Zang (11%) counties were lower than non-minority counties (61%). Docp1000 in 33% and 50% of Yi and Zang ethnic counties decreased, respectively. Nurp1000 in Yi (240%) and other ethnic minority (316%) counties increased faster than non-minority counties (198%). The Theil index for beds and nurses declined, while the index for doctors increased. Key factors driving increases in bed allocation include preferential policies and economic development levels, while health practitioner income, economic development levels and geographical environment significantly influence doctor and nurse allocation. CONCLUSIONS: Preferential policies have been successful in increasing the number of beds in health facilities, but not healthcare workers, in ethnic minority regions. The ethnic disparities in doctor allocation increased in Sichuan Province. To increase the number of doctors and nurses in ethnic minority and poverty-stricken regions, particularly in Yi counties, more preferential policies and resources should be introduced.

Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections.

Objective: Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing to this function remain enigmatic. Here, we aim to test the role of neurons expressing GLP-1 receptors (GLP-1R) in the dorsolateral septum (dLS; dLS GLP-1R ) and their downstream projections on food intake and determine the relationship with feeding regulation. Methods: Using chemogenetic manipulations, we assessed how activation or inhibition of dLS GLP-1R neurons affected food intake in Glp1r-ires-Cre mice. Then, we used channelrhodopsin-assisted circuit mapping, chemogenetics, and electrophysiological recordings to identify and assess the role of the pathway from dLS GLP-1R neurons to the lateral hypothalamic area (LHA) in regulating food intake. Results: Chemogenetic inhibition of dLS GLP-1R neurons increases food intake. LHA is a major downstream target of dLS GLP-1R neurons. The dLS GLP-1R →LHA projections are GABAergic, and chemogenetic inhibition of this pathway also promotes food intake. While chemogenetic activation of dLS GLP-1R →LHA projections modestly decreases food intake, optogenetic stimulation of the dLS GLP-1R →LHA projection terminals in the LHA rapidly suppressed feeding behavior. Finally, we demonstrate that the GLP-1R agonist, Exendin 4 enhances dLS GLP-1R →LHA GABA release. Conclusions: Together, these results demonstrate that dLS-GLP-1R neurons and the inhibitory pathway to LHA can regulate feeding behavior, which might serve as a potential therapeutic target for the treatment of eating disorders or obesity. Highlights: Chemogenetic inhibition of dLS GLP-1R neurons boosts food intake in mice dLS GLP-1R neuron activation does not alter feeding, likely by collateral inhibition dLS GLP-1R neurons project to LHA and release GABA Activation of dLS GLP-1R →LHA axonal terminals suppresses food intake GLP-1R agonism enhances dLS GLP-1R →LHA GABA release via a presynaptic mechanism.

Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota.

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

Magnetic resonance imaging-based rim enhancement could effectually predict poor prognosis in hepatocellular carcinoma: a meta-analysis.

Recent studies have initially shown that MRI-based rim enhancement associates with poor prognosis in hepatocellular carcinoma (HCC) patients, but their sample sizes are small, leading to a necessary of comprehensive analyses to make a relatively solid statement. Thus, this meta-analysis aimed to summarize the correlation between MRI-based rim enhancement and prognosis in HCC patients. Until March 2023, a literature search was conducted on Web of Science, PubMed, EMBASE, Cochrane, CNKI, Wangfang, and CQVIP databases in order to identify studies that report the correlation between MRI-based rim enhancement and the prognosis of HCC patients. MRI-based rim enhancement and prognostic data were extracted and analyzed. In our study, eight studies containing 1816 HCC patients were analyzed. Generally, the presence of MRI-based rim enhancement was related to shortened disease-free survival (DFS) [hazard ratio (HR): 2.77, 95% confidence interval (CI): 2.11-3.62, P < 0.001], and worse overall survival (OS) (HR: 5.43, 95% CI: 2.14-13.79, P < 0.001). While no other prognostic data could be retrieved. Funnel plots, Begg's test, and Egger's test all indicated that no publication bias existed; and the risk score by Newcastle-Ottawa Scale criteria ranged from 7-9 points, suggesting a generally low risk of bias. Meanwhile, the sensitivity analysis showed that the significant findings did not change by omitting each study. Then, subgroup analyses revealed that no matter stratified by tumor size, treatment option, or sample size, rim enhancement was linked with unsatisfied DFS (all P < 0.05). Conclusively, MRI-based rim enhancement could effectually estimate poor survival in HCC patients, indicating its good prognostic value.

Differential Dominance of Ecological Processes Shapes the Longhorn Beetle Community in Tropical Rainforests and Temperate Forests of Southwest China.

(1) Background: Understanding the relationship between community assembly and species coexistence is key to understanding ecosystem diversity. Despite the importance of wood-boring longhorn beetles (Cerambycidae) in forests, factors affecting their population dynamics, species richness, and ecological interactions remain underexplored. (2) Methods: We surveyed cerambycid beetles and plants within five plots each across three transects in tropical rainforests and temperate forests of Yunnan, China, known for its rich biodiversity and varied elevation gradients. We explored a range of analytical tools, including α-diversity comparisons, distance-decay relationships, redundancy analysis, ß-dissimilarity metrics, and various neutral community model analyses. (3) Results: The results revealed a stark contrast between the two forest types: the tropical rainforests hosted 212 Cerambycidae and 135 tree species, whereas the temperate forests had only 16 Cerambycidae and 18 tree species. This disparity was attributed to differences in environmental heterogeneity and dispersal limitations. In temperate forests, pronounced environmental variability leads to steeper distance-decay relationships and reduced α-diversity of Cerambycidae, implying stronger dispersal constraints and weaker plant-beetle associations. Conversely, the more homogenous tropical rainforests exhibited stochastic processes that enhanced Cerambycidae diversity and plant-beetle interactions. (4) Conclusions: Our findings underscore that environmental heterogeneity, dispersal limitations, and host-specificity are pivotal in shaping biodiversity patterns in Cerambycidae, with significant variations across climatic zones.

Charge Density-Regulated Microchannel-Based Electrochemiluminescence Sensor for Hydrogen Sulfide Detection with a Highly Efficient Accumulation Strategy.

The electrochemiluminescence (ECL) intensity can be regulated by ionic current passing through the microchannel, which broadened the regulation of the ECL sensors. But in the early reported sensors, the electrostatic repulsion and steric hindrance caused few targets to approach the interface of the microchannel driven by concentration difference, which reduced the detection efficiency and prolonged the detection period. In this study, different accumulation strategies, such as a positive electric field and different polarity electric fields, were designed to accumulate targets in the microchannel. The interaction of azide groups and hydrogen sulfide served as a research model. Hydrogen sulfide can react with the negatively charged azide groups in the microchannel surface to produce positively charged amino groups, decreasing the negative charge density of the microchannel and thus altering the ionic current and ECL intensity. The accumulation of hydrogen sulfide at the microchannel tip can increase the collision probability with azide groups to improve the detection efficiency, and the integration of accumulation and reaction can shorten the detection period to 28 min. The hydrogen sulfide concentration on the microchannel tip accumulated by applying different polarity electric fields was 22.3-fold higher than that accumulated by applying a positive electric field. The selected research model broadened the application range of a microchannel-based ECL sensor and confirmed the universality of the microchannel-based ECL sensor.

Photoelectrochemical Sensor for H2S Based on a Lead-Free Perovskite/Metal-Organic Framework Composite.

Halide perovskites have emerged as a highly promising class of photoelectric materials. However, the application of lead-based perovskites has been hindered by their toxicity and relatively weak stability. In this work, a composite material comprising a lead-free perovskite cesium copper iodide (CsCu2I3) nanocrystal and a metal-organic framework (MOF-801) has been synthesized through an in situ growth approach. The resulting composite material, denoted as CsCu2I3/MOF-801, demonstrates outstanding stability and exceptional optoelectronic characteristics. MOF-801 may serve a dual role by acting as a protective barrier between CsCu2I3 nanocrystals and the external environment, as well as promoting the efficient transfer of photogenerated charge carriers, thereby mitigating their recombination. Consequently, CsCu2I3/MOF-801 demonstrates its utility by providing both stability and a notably high initial photocurrent. Leveraging the inherent reactivity between H2S and the composite material, which results in the formation of Cu2S and structural alteration, an exceptionally sensitive photoelectrochemical sensor for H2S detection has been designed. This sensor exhibits a linear detection range spanning from 0.005 to 100 µM with a remarkable detection limit of 1.67 nM, rendering it highly suitable for precise quantification of H2S in rat brains. This eco-friendly sensor significantly broadens the application horizon of perovskite materials and lays a robust foundation for their future commercialization.

The role of perioperative sedative anesthetics in preventing postoperative delirium: a systematic review and network-meta analysis including 6679 patients.

OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.

Molecular mechanisms underlying the therapeutic effects of Linggui Zhugan decoction in stroke: Insights from network pharmacology and single-cell transcriptomics analysis.

Linggui Zhugan decoction (LZD), a traditional Chinese medicine formula, has demonstrated significant therapeutic effects in managing poststroke cognitive impairment and hemiplegia. However, the precise molecular mechanisms underlying its efficacy remain incompletely elucidated. The active ingredients and target proteins of LZD were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform database, which is specifically designed for traditional Chinese medicine research. The stroke-related genes were obtained from publicly available databases. Protein-protein interaction, enrichment analysis, and single-cell data analysis were conducted to identify key cells, targets, and pathways. Molecular docking was employed to assess the binding affinity between key components and targets. Network pharmacology analysis identified 190 active ingredients and 248 targets in LZD. These targets were significantly enriched in processes and pathways such as cellular response to lipid, orexin receptor pathway, and were significantly associated with Cerebral infarction and Middle Cerebral Artery Occlusion. Intersection analysis with 2035 stroke-related genes revealed 144 potential targets, which exhibited 2870 interactions and were significantly enriched in signaling pathways such as PI3K-AKT single pathway, MAPK single pathway, and tumor necrosis factor single pathway. Gene set variation analysis showed that the targets of LZD exhibited higher enrichment scores in microglia, M2 macrophages, endothelial cells, and neutrophils, while lower enrichment scores were observed in oligodendrocytes. Furthermore, molecular docking demonstrated a strong binding affinity between key active ingredients and targets. Network pharmacology and single-cell sequencing analysis elucidated the key cells, pathways, targets, and components involved in the therapeutic mechanism of LZD for the treatment of stroke.

Maternal and neonatal outcomes for kidney transplant recipients.

OBJECTIVE: To report pregnancy outcomes for women with kidney transplantation and investigate whether different intervals after transplantation have different effects on pregnancy outcomes. METHODS: A single-center retrospective study was performed. Based on intervals after transplantation, pregnant women with kidney transplantation are divided into two groups: intervals <5 years and ≧5 years. The maternal and neonatal outcomes were compared between the two groups. RESULTS: No maternal and neonatal deaths occurred. The average age of mothers during pregnancy was 32.3 ± 4.1 years and they had a functioning transplant for 4 (interquartile ranges, 3, 6) years. Preeclampsia occurs in sixteen (16.5 %) pregnancies and gestational diabetes (GDM) occurs in twenty (20.6 %). Eighty-eight newborns (90.7 %) had a gestational age of <37 weeks. The average gestational age for live births was 33.8 ± 2.2 weeks and the average birth weight was 2285.6 ± 581.8 g. Neonatal respiratory distress syndrome (NRDS) occurs in fifty-one babies (52.6 %), intraventricular hemorrhage (ICH) occurs in twenty-nine (29.8 %), atrial septal defects (ASD) occurs in thirty-two (32.9 %) and bronchopulmonary dysplasia (BPD) occurs in seven (7.2 %). Further analysis, pregnancy results, including pre-eclampsia, hypertension or GDM, did not differentiate between the two groups (intervals <5 years vs. ≧5 years). Neonatal outcomes, including premature delivery, low birth weight, mode of birth, small for gestational age (SGA), RDS, ICH, ASD, BPD were not distinguishable between the two groups (intervals <5 years vs. ≧5 years). The level of neonatal blood creatinine after birth was linearly related to high maternal creatinine, and can drop to normal levels within a week. CONCLUSIONS: The incidence of maternal and neonatal complications in pregnancies following kidney transplantation is still high, despite the success of most pregnancies. Various posttransplant intervals had no significant impact on pregnancy outcomes.

Combined Therapy of Paravertebral Nerve Pulsed Radiofrequency and Subcutaneous Block for Acute/Subacute Herpetic Neuralgia: A Retrospective Study.

OBJECTIVES: This retrospective study aimed to investigate the effectiveness and safety of early combined therapy with CT-guided paravertebral nerve (PVN), pulsed radiofrequency (PRF), and subcutaneous block on acute/subacute herpes zoster (HZ). METHODS: A total of 98 medical records were analyzed. All patients underwent CT-guided PRF on PVN immediately followed by a single subcutaneous block with lidocaine and dexamethasone in acute/subacute phase. The therapy efficacy was evaluated by pain numeric rating scale (NRS) and effective rate, which was defined as a percent of cases with a reduction in pain NRS>50% at day 1, week 2, 4, 12, and 24 after the procedure. The incidences of medication reduction and postherpetic neuralgia (PHN) were also retrieved. Further comparison was conducted between acute group (disease duration<30 days from HZ onset) and subacute group (30 day50% in prior medications amounted to 83% and the incidence of clinically meaningful PHN decreased to 23%. The clinical efficacy was more profound in acute group than in subacute group at every time points ( P <0.05). No severe complications occurred. DISCUSSION: Our data revealed surprising levels of pain relief by combination therapies of PRF and subcutaneous block targeting different sites of pain pathway, thus suggesting a valuable treatment option for acute/subacute herpetic neuralgia.

Apoptotic body-inspired nanotherapeutics efficiently attenuate osteoarthritis by targeting BRD4-regulated synovial macrophage polarization.

Bromodomain-containing protein 4 (BRD4) is the most well-studied BET protein that is important for the innate immune response. We recently revealed that targeting BRD4 triggers apoptosis in tumor-associated macrophages, but its role in synovial macrophages and joint inflammation is largely unknown. Herein, we demonstrated that BRD4 was highly expressed in the iNOS-positive M1 macrophages in the human and mouse osteoarthritis (OA) synovium, and conditional knockout of BRD4 in the myeloid lineage using Lyz2-cre; BRD4flox/flox mice significantly abolished anterior cruciate ligament transection (ACLT)-induced M1 macrophage accumulation and synovial inflammation. Accordingly, we successfully constructed apoptotic body-inspired phosphatidylserine-containing nanoliposomes (PSLs) loaded with the BRD4 inhibitor JQ1 to regulate inflammatory macrophages. JQ1-loaded PSLs (JQ1@PSLs) exhibited a higher cellular uptake by macrophages than fibroblast-like synoviocytes (FLSs) in vitro and in vivo, as well as the reduction in proinflammatory M1 macrophage polarization. Intra-articular injections of JQ1@PSLs showed prolonged retention within the joint, and remarkably reduced synovial inflammation and joint pain via suppressing M1 polarization accompanied by reduced TRPA1 expression by targeted inhibition of BRD4 in the macrophages, thus attenuating cartilage degradation during OA development. The results show that BRD4-inhibiting JQ1@PSLs can targeted-modulate macrophage polarization, which opens a new avenue for efficient OA therapy via a "Trojan horse".