Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.

Objective To study the effect of the transbrachial artery approach on the success rate of puncture,revascularization time,and postprocedural complications in patients with acute ST-segment elevation myocardial infarction(STEMI)treated by percutaneous coronary intervention(PCI).Methods The clinical data of 324 patients with STEMI who underwent PCI between September 2020 and May 2024 at our hospital were retrospectively analyzed.According to the different approaches,the patients were divided into a brachial artery group(127 cases)and a radial artery group(197 cases).Their procedural parameters(X-ray exposure time,contrast agent dosage,puncture time,puncture success rate,and revascularization time)and hospital length-of-stay,cardiac function indicators,including left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-systolic volume index(LVESVI),and left ventricular end-diastolic volume index(LVEDVI),before surgery and 3 months after PCI,and the incidence of complications were compared between the two groups of patients.Furthermore,a difference-in-differences method was adopted for the logistic model to evaluate the effects of different approaches.Results There were no statistical differences in the general data between the brachial artery group and the radial artery group.Compared with those of the radial artery group,the revascularization time and length-of-stay of the brachial artery group were shortened,and the success rate of puncture was increased(P<0.05).There were no significant differences in X-ray exposure time or contrast agent dosage between the two groups.The changes in LVEF,LVFS,LVESVI,and LVEDVI from baseline to 3 months post-PCI were(10.97±7.15)%,(3.29±5.90)%,(22.11±9.30)mL/m2,and(18.13±6.68)mL/m2,respectively,in the brachial artery group,while those in the radial artery group were(10.61±7.13)%,(4.38±6.04)%,(23.13±9.60)mL/m2,and(19.34±7.27)mL/m2,respectively,without statistical differences.Difference-in-differences analysis revealed that there were no statistical differences in the effects of different approaches on LVEF,LVFS,LVESVI,and LVEDVI between the brachial artery group and the radial artery group.During follow-up,no complications,such as coronary perforation,coronary dissection,or stent thrombosis,were observed in either group,and there were no statistical differences in the complication incidence between the two groups.Conclusion The transbrachial artery approach can shorten the revascularization time and length-of-stay of patients with STEMI treated by PCI.It has a high success rate of puncture and can promote the recovery of postoperative cardiac function without increasing postoperative complications.

Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Objective:To investigate the levels of brain natriuretic peptide(BNP),angiotensin Ⅱ(AngⅡ)and Apelin in hypertensive patients with heart failure and their correlation with cardiac function.Methods:A total of 110 pa-tients with hypertension and heart failure(observation group),110 hypertensive patients(hypertension control group)and 100 healthy subjects undergoing physical examination simultaneously(healthy control group)admitted to Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences between January 2021 and Oc-tober 2022 were enrolled.BNP,AngⅡ and Apelin levels were compared among above-mentioned groups.Pearson correlation analysis was employed to analyze association of above indexes with cardiac function.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of BNP,AngⅡ and Apelin combination for hy-pertension combined heart failure.Results:Compared with participants in healthy control group and hypertension control group,those in observation group had significant higher BNP,AngⅡ,Apelin and left ventricular end-dias-tolic diameter(LVEDd),and significant lower left ventricular ejection fraction(LVEF)(P＜0.001 all).Pearson correlation analysis showed that BNP,AngⅡ,Apelin were negatively correlated with LVEF(r=-0.607,-0.517,-0.549,P＜0.001 all),while they were positively correlated with LVEDd(r=0.695,0.676,0.677,P＜0.001 all).Compared with patients in class Ⅱ and class Ⅲ groups,those in class Ⅳ group had significant higher BNP[(501.42±65.58)pg/ml vs.(382.59±49.69)pg/ml vs.(409.58±53.58)pg/ml],AngⅡ[(3.24±0.84)ng/ml vs.(0.85±0.24)ng/ml vs.(1.06±0.41)ng/ml],Apelin[(6.53±0.71)pg/ml vs.(3.55±0.29)pg/ml vs.(4.98±0.56)pg/ml](P＜0.001 all).ROC curve indicated that the AUC of the combined diagnosis of BNP,AngⅡ and Apelin for hypertensive patients with heart failure of class Ⅲ～Ⅳ was 0.943(95％CI 0.882～0.978),which was significantly higher than that of single index(Z=2.960,6.099,4.653,P＜0.01 all).Conclusion:BNP,AngⅡ and Apelin combination has good performance in diagnosing hypertension complicated heart failure.

Endometriosis presents a common challenge in global women's health.Ferroptosis,as an emerging form of regulated cell death,has recently attracted attention in relation to endometriosis.In terms of disease mechanisms,ferroptosis drives ovarian endometrial fibrosis via the induction of iron overload,and promotes disease progression by regulating multiple signaling pathways,such as p38 mitogen-activated protein kinase/signal transducer and activator of transcription 6(p38MAPK/STAT6),promote angiogenesis,autophagy,etc,fueling disease progression.In terms of infertility,ferroptosis affects embryo development and ovarian function,thereby reducing fertility.From a diagnostic perspective,high expression of ferroptosis-related genes provides potential biomarkers for the early diagnosis of endometriosis,effectively distinguishing patients from healthy individuals,and showing important clinical value.In terms of treatment strategies,non-natural compounds such as Erastin,as well as natural compounds such as resveratrol,ursolic acid,and baicalein,have shown potential therapeutic effects in relieving the pathological process and related symptoms of endometriosis.This review comprehensively elucidates the key role of ferroptosis in endometriosis in terms of the disease mechanisms,infertility,diagnosis,and treatment,and explores its potential as a diagnostic biomarker and therapeutic target,thus providing new theoretical support and treatment strategies for the management of endometriosis.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

Objective To investigate the therapeutic effects of interleukin 23p19(IL-23p19) monoclonal antibody in the MRL/lpr lupus-like mouse model. Methods A total of 36 female MRL/lpr mice aged 8 weeks were randomly divided into 6 groups: PBS group (blank control), IgG group (isotype IgG), dexamethasone (DEX) group (positive control), and three IL-23p19 monoclonal antibody treatment groups with different dose gradients: low dose (LD, 1 mg/kg), medium dose (MD, 3 mg/kg), and high dose (HD, 10 mg/kg). Drug intervention began at 12 weeks of age via tail vein injection. Urine protein levels were measured using urine protein test strips; serum anti-dsDNA antibody levels were detected by ELISA; serum creatinine and blood urea nitrogen levels were measured using an automatic biochemical analyzer; renal histopathological changes were analyzed by H&E and PAS staining; immunofluorescence was used to assess IgG and C3 immune complex deposition in kidney tissues; flow cytometry was employed to examine the expression of T helper 1(Th1), Th2, Th17, T follicular helper (Tfh), and regulatory T cells(Treg) cell subsets in the spleen; and RT-qPCR was used to detect the expression of related transcription factors in the spleen. Results IL-23p19 monoclonal antibody reduced urine protein levels, alleviated splenomegaly, improved renal function, and decreased anti-dsDNA antibody levels in MRL/lpr mice. It also mitigated glomerulonephritis and reduced renal immune complex deposition. Furthermore, IL-23p19 monoclonal antibody significantly suppressed the proportion of Th1 and Th17 cells while upregulating Treg cell proportion in the spleen. Additionally, it downregulated T-bet and retinoic acid receptor-related orphan receptor γt (RORγt) mRNA levels and upregulated forkhead box P3(FOXP3) mRNA levels in the spleen. Conclusions IL-23p19 monoclonal antibody demonstrates significant therapeutic effects in MRL/lpr mice, likely through modulation of the Th17/Treg cell balance.
Animals ; Female ; Mice, Inbred MRL lpr ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Antibodies, Monoclonal/therapeutic use* ; Interleukin-23 Subunit p19/immunology* ; Mice ; Lupus Nephritis/drug therapy* ; Kidney/drug effects* ; Antibodies, Antinuclear/blood*