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.

Objective To construct Pseudomonas aeruginosa(PA)strain with deletion of the pyocyanin synthesis gene PAOⅡ and investigate its drug resistance.Methods By analyzing the ge-nome of the PAOⅡ genotype strain of PA,the distribution of genes/gene clusters related to pyocyanin synthesis in the genome was explored.A strain with deletion of the pyocyanin synthesis gene phzM was constructed using homologous recombination-based seamless gene knockout technology.The growth and drug tolerance of the wild-type and mutant strains were compared.Results Kyoto Encyclopedia of Genes and Genomes(KEGG)clustering analysis was performed on the website https://www.kegg.jp/.The results revealed a gene cluster composed of 9 genes(including PhzA,PhzB,PhzC,PhzD,PhzE,PhzF,PhzG,phzM and PhzS),which was completely consistent with the KEGG PATHWAY:Phenazine biosynthesis-M00835 Pyocyanine biosynthesis pathway.The key gene phzM for pyocyanin synthesis was knocked out via homologous recombination.After the exchange,monoclonal strains growing on M9-citrate medium were verified using primers phzM-AF and phzM-BR.The shuttle plasmid pK18mobSacB-phzM-AB was successfully transfected into the PAOⅡ genotype strain.After gene ex-change,monoclonal strains capable of growing on antibiotic-free plates were selected,and polymerase chain reaction(PCR)was performed to obtain strains with successful scarless knockout of the phzM gene.At 3 and 6 days of culture,the biofilm formation thickness of the PAOⅡ genotype strain was greater than that of the PAOⅡ-△phzM strain,with a statistically significant difference(P＜0.05).Conclusion The biofilm synthesis capacity of the pyocyanin synthesis-deficient strain is reduced,and its resistance to cephalosporins(ceftazidime)is also decreased.

Pancreatic cancers (PCs) is a common malignant tumor with poor prognosis in the digestive system. Its main treatment methods include surgery, radiotherapy, chemotherapy, and targeted therapy. The early diagnosis rate of hidden onset of PCs is low, and most patients have already lost the opportunity to undergo surgery when diagnosed with PCs. Chemotherapy is still the main treatment for advanced PCs, but the use of chemotherapy drugs in PCs can easily lead to drug resistance. The most significant feature that distinguishes PCs from other tumors is its rich and dense matrix, which not only hinders drug penetration but also impedes the infiltration of immune cells. The above reasons have led to a very low survival rate of PCs patients. Therefore, drug delivery systems are very important in the diagnosis and treatment of PCs. They can improve drug delivery, enhance biological barrier penetration, reduce side effects, and combine multiple treatment methods. Therefore, the treatment prospects of PCs are very broad. Currently, drug delivery systems widely applied in PCs primarily include nanodrug delivery systems, tumor microenvironment-targeted drug delivery system, immunotherapy drug delivery system, gene therapy drug delivery system, and combination therapy drug delivery system that synergize multiple therapeutic modalities. Emerging drug delivery systems (DDSs) have revolutionized PCs treatment by addressing these challenges through multiple mechanisms. Nanoformulations improve drug solubility, prolong circulation time, and reduce systemic toxicity via passive/active targeting. Smart DDSs responsive to PCs-specific stimuli enable extracellular matrix degradation, tumor-associated fibroblasts reprogramming, and vascular normalization to enhance drug accessibility. Last but not least, carrier systems loaded with myeloid-derived suppressor cell inhibitors or T cell activators can reverse immunosuppression and potentiate immunotherapy efficacy. Advanced platforms co-deliver chemotherapeutics with immunomodulators, gene-editing tools, or sonodynamic agents to achieve synergistic antitumor effects. These platforms aim to address critical challenges in PCs treatment, such as enhancing drug bioavailability, overcoming stromal barriers, reprogramming immunosuppressive niches, and achieving multi-mechanistic antitumor effects. This article provides a systematic summary and prospective analysis of the current development status, latest cutting-edge advances, opportunities, and challenges of the above-mentioned drug delivery systems in the field of PCs therapy.

Objective To investigate the clinical value of 3.0 T functional magnetic resonance imaging in evaluating postoperative recurrence and treatment efficacy of glioma. Methods A retrospective analysis was conducted on the general clinical data of 67 patients who underwent glioma surgery at the Second Affiliated Hospital of Xingtai Medical University. All patients received chemotherapy for more than one month post-surgery. Recurrence of glioma was diagnosed based on secondary surgery or pathological biopsy results as the gold standard. From 3 to 6 months post-surgery, computerized tomography was used to measure cerebral blood volume (CBV), three-dimensional arterial spin labeling was used to measure cerebral blood flow (CBF) and relative CBF (rCBF), and diffusion-weighted imaging with and without contrast enhancement was used to measure apparent diffusion coefficient (ADC). Data were analyzed using SPSS 26.0 statistical software, and the t test or χ² test was used for inter-group comparisons based on data type. The receiver operating characteristic (ROC) curve was applied to evaluate the value of CBV, rCBF, and ADC in assessing postoperative recurrence and treatment efficacy of glioma. Results Patients with high-grade gliomas showed significantly higher CBV and rCBF and significantly lower ADC compared to those with low-grade gliomas (P < 0.05). The area under the ROC curve (AUC) of CBV, rCBF, and ADC in combination for grading glioma was 0.960, which was higher than those of individual indicators (0.790, 0.955, and 0.795, P < 0.05). The recurrence group had significantly higher CBV and rCBF and lower ADC compared to the non-recurrence group (P < 0.05). The AUC of CBV, rCBF, and ADC in combination for predicting postoperative glioma recurrence was 0.965, which was significantly higher than those of individual indicators (0.729, 0.929, and 0.941, P < 0.05). CBV and rCBF were lower and ADC was higher in the effective treatment group than in the ineffective treatment group (P < 0.05). The AUC of CBV, rCBF, and ADC in combination for evaluating glioma treatment efficacy was 0.985, which was higher than those of individual indicators (0.842, 0.898, and 0.961, P < 0.05). Conclusion The CBV, rCBF, and ADC in combination has shown high diagnostic accuracy and predictive efficacy in the evaluation of postoperative recurrence and treatment efficacy of glioma, which has important clinical application value.

This review described the potential health threats to the cardiovascular system from micro-nano plastics (MNPs) and their multifaceted toxicity mechanisms. The article reviewed the environmental distribution of MNPs, exposure pathways, and their toxic effects on the cardiovascular system, and summarized the specific mechanisms of MNPs involving oxidative stress, inflammatory response, mitochondrial damage, apoptosis, pyroptosis, and autophagy dysregulation. Meanwhile, the combined toxic effects of MNPs with other environmental pollutants (e.g., heavy metals and polycyclic aromatic hydrocarbons), including synergistic, antagonistic, and dual effects, were analyzed, and the potential risks of MNPs as carriers of microorganisms and toxic chemicals were pointed out. The widespread presence of MNPs and their complex toxicity mechanisms may make them important triggers for cardiovascular diseases, but current research still suffers from unbalanced studies across environmental systems, incomplete understanding of plastic properties, and limited knowledge of long-term biological effects. Future research should focus on the long-term effects of MNPs, the joint toxicity mechanisms with other pollutants, and the differential effects across population subgroups. It is suggested to accelerate plastic recycling technology innovation, promote biodegradable materials, and optimize waste treatment process to mitigate the potential threat of MNPs pollution to human health. Through multidisciplinary collaboration and in-depth research, combining innovative concepts from toxicology, public health policy, and environmental science, it is expected to provide new methods and approaches for the prevention and treatment of cardiovascular diseases associated with MNPs.

ObjectiveTo investigate the efficacy of Xingpi capsules （XPC） in treating diarrhea-predominant irritable bowel syndrome （IBS-D） with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free （SPF）-grade healthy rats were used as the normal control group. After successful modeling， SPF-grade rats were randomly divided into a model group， a pinaverium bromide group （1.5 mg·kg^-1）， and low- and high-dose XPC groups （0.135 and 0.54 g·kg^-1）， with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage， while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day， and the Bristol score was recorded. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of 5-hydroxytryptamine （5-HT） in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier， intestinal motility， and expression of related pathway proteins were evaluated by hematoxylin-eosin （HE） staining， immunohistochemistry， and Western blot. ResultsCompared with those in the normal control group， rats in the model group showed a significantly decreased body weight and increased diarrhea rate， diarrhea grade， and Bristol score （P<0.01）. HE staining revealed incomplete colonic mucosa in the model group， with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier， shedding and disappearance of microvilli， and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated （P<0.01）， and the levels of 5-HT in serum and colon tissue were elevated （P<0.01）. The small intestine propulsion rate significantly increased （P<0.01）， and the expression of contractile proteins Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 2 （ROCK2） in colon and phosphorylation of myosin light chain （MLC₂₀） were upregulated （P<0.01）. Compared with the model group， the treatment groups showed alleviated diarrhea， diarrhea-associated symptoms， and pathological manifestations of colon tissue to varying degrees. Specifically， high-dose XPC exhibited effectively relieved diarrhea， promoted recovery of colonic mucosal structure， significantly reduced congestion and edema， upregulated expression of Occludin and Claudin-5 （P<0.01）， decreased levels of 5-HT in serum and colon tissue （P<0.05，P<0.01）， significantly slowed small intestine propulsion rate （P<0.01）， and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC₂₀ （P<0.05，P<0.01）. ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction， and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.

Objective The aim of this study was to clarify the role and mechanism of Pseudomonas aeruginosa vaccine subunit OprI in the fusion protein vaccine rePO(PcrV-OprI).Methods The in vitro stability of rePO,PcrV and OprI at 4 ℃,25 ℃,and 37 ℃ was examined.After immunizing mice with rePO,OprI and PcrV,respectively,the specific antibody potency in serum and the proportion of cells secreting IFN-γ and IL-4 in the spleen were examined;Additionally,detection of the levels of protein uptake by DC2.4 cells in vitro using laser confocal microscopy and flow cytometry,and their ability to promote the maturation of mouse bone marrow-derived dendritic cells(BMDC).Results The heat stability of fusion protein rePO was significantly better than that of PcrV.The induced anti-PcrV IgG and anti-OprI IgG potency of rePO was significantly higher than that of monomeric PcrV and OprI.Additionally,the number of cells secreting IFN-γ and IL-4 induced by immunization with rePO was significantly higher than that of PcrV and OprI.The uptake rate of fusion protein rePO by DC2.4 cells was significantly higher than that of PcrV and OprI.Furthermore,rePO promoted the maturation of mouse BMDC more effectively than PcrV and OprI.Conclusion OprI in the fusion protein rePO can significantly improve its thermal stability and immunogenicity,which lays the foundation for the successful development of Pseudomonas aeruginosa vaccine.

Objective To observe the value of diffusion-weighted imaging(DWI)parameters for evaluating grade of gliomas.Methods Totally 116 patients with glioma were retrospectively enrolled and divided into low-grade group(Ⅰ—Ⅱ,n=66)and high-grade group(Ⅲ—Ⅳ,n=50)according to 2000 WHO tumor grading criteria.Clinical and DWI data,including Ki-67 labeling index(LI),apparent diffusion coefficient(ADC),exponential ADC(EADC)and relative ADC(rADC)were compared between groups.The correlations of ADC,EADC and rADC with Ki-67 LI were explored,and the efficacy of above indexes for evaluating grade of glioma was analyzed.Results Significant differences of Ki-67 LI,ADC,EADC and rADC were found between groups(all P＜0.05).ADC and rADC of glioma were negatively correlated(r=-0.565,-0.625,both P＜0.05),while EADC was positively correlated with Ki-67 LI(r=0.587,P＜0.05).ADC,EADC,rADC and Ki-67 LI were all impact factors of grade of glioma(all P＜0.05),with the area under the curve of 0.768,0.802,0.788 and 0.793,respectively,and AUC of the combination of the four was 0.874,significantly higher than each index alone(all P＜0.05).Conclusion ADC,EADC and rADC were helpful for evaluating grade of glioma.Combining with Ki-67 LI could further improve diagnostic efficacy.

Objective:To explore the clinical application of transurethral steam thermal ablation of the prostate as an ultra-minimally invasive treatment of benign prostatic hyperplasia(BPH).Methods:We treated 18 BPH patients by transurethral steam thermal ablation of the prostate in our hospital,and followed them up for 6-12 months after operation.We obtained the IPSS,maxi-mum urinary flow rate(Qmax),IIEF-5 scores,Male Sexual Health Questionnaire-Ejaculatory Dysfunction-Short Form(MSHQ-EjD-SF)scores and quality of life(QOL)scores from the patients and compared them before and after surgery.Results:Operations were successfully completed in all the cases,with no intraoperative complications,and all the patients were discharged on the second day after surgery.At the 6-month follow-up after surgery,the Qmax increased from(10.08±2.06)ml/s before surgery to(7.51±3.21)ml/s,the IPSS decreased from 23.72±1.87to8.06±1.39,and the QOL score decreased from 5.11±0.58 before sur-gery to 1.28±0.46.The differences in these indicators were statistically significant(P＜0.05).And these is no significant differ-ence in the MSHQ-EjD-SF and IIEF-5 score(P＞0.05).Conclusion:Transurethral steam thermal ablation of the prostate is a safe,effective and almost non-invasive surgical strategy for the treatment of BPH,with a good prospect of clinical application.

AIM To investigate the effects of Yiqi Juanbi Formula on chondrocyte pyroptosis in rat models of collagen-induced arthritis(CIA).METHODS Fifty rats were subcutaneously injected at the tail base with an emulsion containing equal volumes of bovine type Ⅱ collagen and incomplete Freund's adjuvant(IFA)to establish the CIA models.These rats were then randomly assigned to the model group,the methotrexate group(0.35 mg/kg),and the low-dose,medium-dose,and high-dose Yiqi Juanbi Formula groups(9.4,18.7,37.4 g/kg),in contrast to the ten intact rats serving in the normal control group.Following four weeks of intragastric administration,the rats had their general conditions observed;their joint swelling and arthritis indices measured;their ankle joint pathology assessed by HE staining;their serum levels of IL-1β,IL-18 and TNF-ɑ detected by ELISA;their mRNA expressions of NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ in ankle cartilage quantified by RT-qPCR;their protein expressions of NF-κB,NLRP3 and Caspase-1 in ankle cartilage analyzed by Western blot;and their NLRP3 and GSDMD positive expressions in ankle cartilage examined by immunohistochemistry.RESULTS Compared to the control group,the model group showed significantly increased joint swelling and arthritis indices(P＜0.01);elevated serum levels of IL-1 β,IL-18 and TNF-ɑ(P＜0.01);pathological changes including cartilage surface defects,reduced cell count,altered cellular morphology,irregular cell arrangement,and significant inflammatory cell infiltration in synovial tissue;upregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.01)and increased protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.01)in ankle cartilage;enhanced positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).Compared to the model group,the groups intervened with methotrexate or medium-or high-dose Yiqi Juanbi Formula exhibited reduced joint swelling and arthritis indices(P＜0.01);alleviated pathological damage in ankle joints;decreased serum levels of IL-1β,IL-18 and TNF-ɑ(P＜0.01);downregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.05,P＜0.01),and reduced protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.05,P＜0.01)in ankle cartilage;and diminished positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).CONCLUSION Yiqi Juanbi Formula alleviates inflammation in CIA rats,potentially by inhibiting the activation of the NF-κB/NLRP3/Caspase-1 signaling pathway,thereby suppressing chondrocyte pyroptosis.