Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Objective:To analyze the relationship between serum GATA binding protein-3(GATA3)and eosinophilic cationic protein(ECP)and lung function indexes in children with obliterated bronchiolitis and their predictive value for poor prognosis.Methods:96 children with bronchiolitis obliterans admitted to our hospital from January 2022 to July 2024 were divided into mild group(34 cases)and moderate to severe group(62 cases)according to their severity.Serum GATA3,ECP levels and lung function indexes were detected in the two groups,and Pearson correlation was used to analyze the correlation between serum GATA3,ECP levels and lung function indexes.According to the levels of serum GATA3 and ECP,they were divided into high GATA3 group and low GATA3 group,high ECP group and low ECP group.The incidence of adverse prognosis in different groups was compared.Area under ROC curve(AUC)was used to evaluate the predictive efficacy of serum GATA3 combined with ECP for poor prognosis.Results:The levels of serum GATA3 and ECP in moderate and severe group were higher than those in mild group(P＜0.05).By Pearson correlation analysis,serum GATA3 and ECP levels were negatively correlated with tidal volume(VT),peak-to-expiratory volume(VPEFNE)and peak-to-time ratio(TPTEF/TE)in children with bronchiolitis obliterans(P＜0.05).The incidence of adverse prognosis in the high GATA3 group was higher than that in the low GATA3 group,and the incidence of adverse prognosis in the high ECP group was higher than that in the low ECP group(P＜0.05).ROC curve analysis showed that serum GATA3 combined with ECP had a sensitivity of 90.45％,specificity of 52.37％and AUC of 0.893 in predicting adverse prognosis of children with bronchiolitis obliterans.Conclusion:Serum GATA3 and ECP are closely related to pulmonary function indexes in children with bronchiolitis obliterans.The combined effect of GATA3 and ECP is better in predicting poor prognosis,and it has a certain suggestive role in evaluating the disease.

Objective:To analyze the relationship between serum GATA binding protein-3(GATA3)and eosinophilic cationic protein(ECP)and lung function indexes in children with obliterated bronchiolitis and their predictive value for poor prognosis.Methods:96 children with bronchiolitis obliterans admitted to our hospital from January 2022 to July 2024 were divided into mild group(34 cases)and moderate to severe group(62 cases)according to their severity.Serum GATA3,ECP levels and lung function indexes were detected in the two groups,and Pearson correlation was used to analyze the correlation between serum GATA3,ECP levels and lung function indexes.According to the levels of serum GATA3 and ECP,they were divided into high GATA3 group and low GATA3 group,high ECP group and low ECP group.The incidence of adverse prognosis in different groups was compared.Area under ROC curve(AUC)was used to evaluate the predictive efficacy of serum GATA3 combined with ECP for poor prognosis.Results:The levels of serum GATA3 and ECP in moderate and severe group were higher than those in mild group(P＜0.05).By Pearson correlation analysis,serum GATA3 and ECP levels were negatively correlated with tidal volume(VT),peak-to-expiratory volume(VPEFNE)and peak-to-time ratio(TPTEF/TE)in children with bronchiolitis obliterans(P＜0.05).The incidence of adverse prognosis in the high GATA3 group was higher than that in the low GATA3 group,and the incidence of adverse prognosis in the high ECP group was higher than that in the low ECP group(P＜0.05).ROC curve analysis showed that serum GATA3 combined with ECP had a sensitivity of 90.45％,specificity of 52.37％and AUC of 0.893 in predicting adverse prognosis of children with bronchiolitis obliterans.Conclusion:Serum GATA3 and ECP are closely related to pulmonary function indexes in children with bronchiolitis obliterans.The combined effect of GATA3 and ECP is better in predicting poor prognosis,and it has a certain suggestive role in evaluating the disease.

Objective To compare the pharmacokinetics of crushed posaconazole enteric-coated tablets and oral suspension after intragastric administration in rabbits.Methods The experiment was designed in a randomized cross-over study.Six New Zealand rabbits were intragastrically administrated with crushed posaconazole enteric-coated tablets or suspension,and blood was collected at specific time points.The concentration of posaconazole in plasma was determined by high-performance liquid chromatography,and the pharmacokinetic parameters of both groups were calculated with DAS 2.0 software.Results The main pharmacokinetic parameters of posaconazole enteric-coated tablets and suspension were obtained as follows:AUC0-twere(40.03±5.04)and(49.92±16.09)μg·mL-1·h;AUC0-∞ were(44.00±4.50)and(51.10±16.80)μg·mL-1·h;t1/2 were(7.30±1.13)and(8.53±1.34)h;Cmrx were(3.12±0.57)and(2.78±0.60)μg·mL-1;apparent volume of distribution(Vd)were(2.40±0.34)and(2.59±0.76)L·kg-1;clearance rate(CL)were(0.23±0.02)and(0.22±0.08)L·h-1·kg.There were no statistic differences in AUC0-t,Cmax and Vd between posaconazole suspension and crushed enteric-coated tablets after intragastric administration(all P＞0.05).Conclusion There was no pharmacokinetic advantage for crushed enteric-coated tablets against oral suspension.

Chinese Expert Consensus on Clinical Application of Tongxinluo in Prevention and Treatment of Coronary Heart Disease strictly follows the consensus formulation specifications,with evidence-based medicine as the main,consensus as the supplement,and experience as the reference,aiming to standardize the reasonable application of Tongxinluo in the treatment of coronary heart disease.In combination with conventional treatment,Tongxinluo can increase clinical benefits for common types of coronary heart disease.

Humans ; Stroke Volume ; Valsartan/therapeutic use* ; Heart Failure/drug therapy* ; Hypotension/drug therapy* ; Aminobutyrates/therapeutic use* ; Drug Combinations ; Angiotensin Receptor Antagonists/therapeutic use* ; Tetrazoles/therapeutic use* ; Treatment Outcome ; Ventricular Function, Left

Humans ; Stroke Volume ; Valsartan/therapeutic use* ; Heart Failure/drug therapy* ; Hypotension/drug therapy* ; Aminobutyrates/therapeutic use* ; Drug Combinations ; Angiotensin Receptor Antagonists/therapeutic use* ; Tetrazoles/therapeutic use* ; Treatment Outcome ; Ventricular Function, Left

OBJECTIVE: To explore the potential mechanism of resistance to axitinib in clear cell renal cell carcinoma (ccRCC), with a view to expanding the understanding of axitinib resistance, facilitating the design of more specific treatment options, and improving the treatment effectiveness and survival prognosis of patients. METHODS: By exploring the half maximum inhibitory concentration (IC₅₀) of axitinib on ccRCC cell lines 786-O and Caki-1, cell lines resistant to axitinib were constructed by repeatedly stimulated with axitinib at this concentration for 30 cycles in vitro. Cell lines that were not treated by axitinib were sensitive cell lines. The phenotypic differences of cell proliferation and apoptosis levels between drug resistant and sensitive lines were tested. Genes that might be involved in the drug resistance process were screened from the differentially expressed genes that were co-upregulated in the two drug resistant lines by transcriptome sequencing. The expression level of the target gene in the drug resistant lines was verified by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB). The expression differences of the target gene in ccRCC tumor tissues and adjacent tissues were analyzed in the Gene Expression Profiling Interactive Analysis (GEPIA) public database, and the impact of the target gene on the prognosis of ccRCC patients was analyzed in the Kaplan-Meier Plotter (K-M Plotter) database. After knocking down the target gene in the drug resistant lines using RNA interference by lentivirus vector, the phenotypic differences of the cell lines were tested again. WB was used to detect the levels of apoptosis-related proteins in the different treated cell lines to find molecular pathways that might lead to drug resistance. RESULTS: Cell lines 786-O-R and Caki-1-R resistant to axitinib were successfully constructed in vitro, and their IC₅₀ were significantly higher than those of the sensitive cell lines (10.99 μmol/L, P < 0.01; 11.96 μmol/L, P < 0.01, respectively). Cell counting kit-8 (CCK-8) assay, colony formation, and 5-ethynyl-2 '-deoxyuridine (EdU) assay showed that compared with the sensitive lines, the proliferative ability of the resistant lines decreased, but apoptosis staining showed a significant decrease in the level of cell apoptosis of the resistant lines (P < 0.01). Although resistant to axitinib, the resistant lines had no obvious new replicated cells in the environment of 20 μmol/L axitinib. Nuclear protein 1 (NUPR1) gene was screened by transcriptome sequencing, and its RNA (P < 0.0001) and protein expression levels significantly increased in the resistant lines. Database analysis showed that NUPR1 was significantly overexpressed in ccRCC tumor tissue (P < 0.05); the ccRCC patients with higher expression ofNUPR1had a worse survival prognosis (P < 0.001). Apoptosis staining results showed that knockdown ofNUPR1inhibited the anti-apoptotic ability of the resistant lines to axitinib (786-O, P < 0.01; Caki-1, P < 0.05). WB results showed that knocking downNUPR1decreased the protein level of B-cell lymphoma-2 (BCL2), increased the protein level of BCL2-associated X protein (BAX), decreased the protein level of pro-caspase3, and increased the level of cleaved-caspase3 in the resistant lines after being treated with axitinib. CONCLUSION ccRCC cell lines reduce apoptosis through theNUPR1 -BAX/ BCL2 -caspase3 pathway, which is involved in the process of resistance to axitinib.
Humans ; Carcinoma, Renal Cell/metabolism* ; Axitinib/pharmacology* ; Kidney Neoplasms/metabolism* ; bcl-2-Associated X Protein ; Nuclear Proteins ; Cell Line, Tumor ; Apoptosis ; Cell Proliferation

Neuropathic pain(NP) has similar phenotypes but different sequential neuroinflammatory mechanisms in the pathological process. It is of great significance to inhibit the initiation of neuroinflammation, which has become a new direction of NP treatment and drug development in recent years. Mongolian drug Naru-3 is clinically effective in the treatment of trigeminal neuralgia, sciatica, and other NPs in a short time, but its pharmacodynamic characteristics and mechanism of analgesia are still unclear. In this study, a spinal nerve ligation(SNL) model simulating clinical peripheral nerve injury was established and the efficacy and mechanism of Naru-3 in the treatment of NPs was discussed by means of behavioral detection, side effect evaluation, network analysis, and experimental verification. Pharmacodynamic results showed that Naru-3 increased the basic pain sensitivity threshold(mechanical hyperalgesia and thermal radiation hyperalgesia) in the initiation of SNL in animals and relieved spontaneous pain, however, there was no significant effect on the basic pain sensitivity threshold and motor coordination function of normal animals under physiological and pathological conditions. Meanwhile, the results of primary screening of target tissues showed that Naru-3 inhibited the second phase of injury-induced nociceptive response of formalin test in mice and reduced the expression of inflammatory factors in the spinal cord. Network analysis discovered that Naru-3 had synergy in the treatment of NP, and its mechanism was associated with core targets such as matrix metalloproteinase-9(MMP9) and interleukin-1β(IL-1β). The experiment further took the dorsal root ganglion(DRG) and the stage of patho-logical spinal cord as the research objects, focusing on the core targets of inducing microglial neuroinflammation. By means of Western blot, immunofluorescence, agonists, antagonists, behavior, etc., the mechanism of Naru-3 in exerting NP analgesia may be related to the negative regulation of the MMP9/IL-1β signaling pathway-mediated microglia p38/IL-1β inflammatory loop in the activation phase. The relevant research enriches the biological connotation of Naru-3 in the treatment of NP and provides references for clinical rational drug use.
Rats ; Mice ; Animals ; Matrix Metalloproteinase 9/metabolism* ; Rats, Sprague-Dawley ; Neuroinflammatory Diseases ; Interleukin-1beta/metabolism* ; Spinal Cord/metabolism* ; Signal Transduction ; Hyperalgesia/metabolism* ; Neuralgia/metabolism*

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal