ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

The study explored the therapeutic effect and mechanism of the compound composed of tangerine peel,plum,agrimony and hawthorn on Eimeria tenella in chicks.In the experiment,144 chicks were divided into six groups:the blank group,the model group,the diclazuril group,and the high-dose,medium-dose and low-dose traditional Chinese medicine compound groups.The 14-day-old chickens were infected,the body weight and mortality were recorded,and the samples were dis-sected at 21 days of age.The anticoccidial effect of Chenpi compound at different doses was evalua-ted by calculating anticoccidial index,feed conversion rate and detecting serum cytokine levels and related mRNA expression levels.The results showed that the anticoccidial index of the middle dose group was 172.86,and the anticoccidial index of the low dose group was 158.98.In the middle and low dose groups,the levels of IL-1β,IL-6 and MDA in serum decreased significantly,while the levels of IL-4,IL10,T-AOC,SOD,CAT and GSH-Px increased significantly,and the mRNA ex-pression levels of related inflammation and antioxidant pathways changed.Further studies found that the medium-dose compound can regulate the ChTLR15/ChMyD88/ChNF-κB/ChNLRP3/Caspase-1 inflammatory signaling pathway,activate the Nrf2/Keap1/HO-1 antioxidant signaling pathway,and enhance the body's anti-inflammatory and antioxidant capacity;at the same time,it can increase the expression of intestinal tight junction ZO-1 and Occludin,repair the damaged in-testinal barrier,and play an anticoccidial role.The results showed that the middle dose of tangerine peel compound had a good effect in the treatment of coccidiosis,and its mechanism involved the regulation of anti-inflammatory and antioxidant pathways.

Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P＜0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P＜0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P＜0.05;1 g·L-1:P＜0.01;3 g·L-1:P＜0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P＜0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.

The study explored the therapeutic effect and mechanism of the compound composed of tangerine peel,plum,agrimony and hawthorn on Eimeria tenella in chicks.In the experiment,144 chicks were divided into six groups:the blank group,the model group,the diclazuril group,and the high-dose,medium-dose and low-dose traditional Chinese medicine compound groups.The 14-day-old chickens were infected,the body weight and mortality were recorded,and the samples were dis-sected at 21 days of age.The anticoccidial effect of Chenpi compound at different doses was evalua-ted by calculating anticoccidial index,feed conversion rate and detecting serum cytokine levels and related mRNA expression levels.The results showed that the anticoccidial index of the middle dose group was 172.86,and the anticoccidial index of the low dose group was 158.98.In the middle and low dose groups,the levels of IL-1β,IL-6 and MDA in serum decreased significantly,while the levels of IL-4,IL10,T-AOC,SOD,CAT and GSH-Px increased significantly,and the mRNA ex-pression levels of related inflammation and antioxidant pathways changed.Further studies found that the medium-dose compound can regulate the ChTLR15/ChMyD88/ChNF-κB/ChNLRP3/Caspase-1 inflammatory signaling pathway,activate the Nrf2/Keap1/HO-1 antioxidant signaling pathway,and enhance the body's anti-inflammatory and antioxidant capacity;at the same time,it can increase the expression of intestinal tight junction ZO-1 and Occludin,repair the damaged in-testinal barrier,and play an anticoccidial role.The results showed that the middle dose of tangerine peel compound had a good effect in the treatment of coccidiosis,and its mechanism involved the regulation of anti-inflammatory and antioxidant pathways.

OBJECTIVE To observe the effects of measures dominated by intensifying link quality on prevention and control of carbapenem-resistant Klebsiella pneumoniae(CRKP)among general ICU patients.METHODS The conventional intervention measures were taken from Jan.2016 to Oct.2020,which was assigned as the pre-inter-vention period;the intervention measures dominated by enhancement of link quality were taken for the general ICU patients(the study group)from Nov.2020 to Oct.2021,which was set as the intervention period,the inter-vention measures were taken for the neurosurgery ICU patients and the surgery ICU patients(the control group).A two-group interrupted time series of a quasi-experimental study was analyzed,and whether or not the intervention measures could reduce the incidence of CRKP hospital-associated infection among the general ICU patients was evaluated.RESULTS A total of 23 713 case-times of patients from three ICU wards were enrolled in the study.The incidence of CRKP hospital-associated infection among the general ICU patients was 4.49 cases per thousand patient-days during intervention period,3.71 cases per thousand patient-days during pre-intervention pe-riod,and there was no significant difference(u=-1.412,P=0.079);it was lower than 7.06 cases per thousand patient-days during nearly one year before the intervention period(from Nov.2019 to Oct.2020),and there was significant difference(u=3.128,P=0.002).The result of analysis of the interrupted time series showed that there was significant difference in the slope change between the study group and the control group after the inter-vention(P=0.035),indicating that the intervention measures could reduce the incidence of CRKP hospital-associ-ated infection in the study group,and there was significant difference in the changing trend between the study group and the control group.CONCLUSIONS The prevention and control measures for CRKP dominated by the link quality management can effectively reduce the incidence of CRKP hospital-associated infection among the gen-eral ICU patients.The prevention and control strategies may provide reference for prevention and control of CRKP in ICUs of other medical institutions.

Objective To investigate the efficacy and safety of domestic RECO flow restoration device in endovascular treatment of acute ischemic stroke(AIS)patients in a real-world setting.Methods From January 2019 to June 2021,consecutive patients with acute intracranial vessel occlusion treated with RECO device from 8 stroke centers in Jiangsu Province were analyzed retrospectively.Baseline and clinical data were collected,including age,gender,baseline modified Rankin scale(mRS)scores,National Institutes of Health stroke scale(NIHSS)score on admission,trial of Org 10172 in acute stroke treatment(TOAST)classification,responsible location of occlusion,wake-up stroke,and medical history(hypertension,diabetes mellitus,hyperlipidemia,atrial fibrillation,coronary heart disease,peripheral arterial disease),smoking,and alcohol consumption.Furthermore,surgical parameters were collected,including time indicators(intervals between symptom onset,admission,puncture and recanalization),preoperative intravenous thrombolysis,general anesthesia,combination of aspiration,number of passes,first pass effect(modified thrombolysis in cerebral infarction[mTICI]grade 3 achieved with s single stent-based thrombectomy),rescue therapy(including thrombectomy with other stents,intra-arterial urokinase thrombolysis,intra-arterial application of tirofiban,emergency angioplasty[stent implantation,balloon dilatation,balloon dilatation combined with stent implantation]),balloon guided catheter and NIHSS score at discharge.The effectiveness indicators included immediate successful recanalization after the operation(mTICI grade ≥ 2b),complete recanalization(mTICI grade 3),and a good prognosis at 90 d after the operation(mRS score ≤2).The safety indicators included symptomatic intracranial hemorrhage(sICH)within 24 h after the operation,device-related intraoperative complications(such as thrombus escape,iatrogenic dissection,bleeding at the surgical site),and all-cause mortality within 90 days after the operation.All patients were divided into the anterior circulation occlusion group and the posterior circulation occlusion group according to the location of the responsible occluded vessel,and the effectiveness and safety indexes were analyzed.Results A total of 366 patients with AIS caused by intracranial vessel occlusion who underwent mechanical thrombectomy with the domestic RECO thrombectomy stent were included.The average age was(69±11)years,with 54 patients(14.8％)over 80 years old and 221 patients(60.4％)male.There were 296 patients in the anterior circulation occlusion group and 70 patients in the posterior circulation occlusion group.(1)Immediate successful recanalization(mTICI grade≥2b)was achieved in 337 patients(92.1％),and complete recanalization was achieved in 282 patients(77.0％)immediately after the operation.The average number of thrombectomies was(1.9±1.0)times,and 141 patients(38.5％)achieved recanalization on the first attempt.9 patients(2.5％)used other stents during the operation,and 65 patients(17.8％)underwent emergency angioplasty.The incidence of sICH within 24 h after the operation was 10.9％(40/366),the good prognosis rate at 90 d after the operation was 53.6％(196/366),and the all-cause mortality rate at 90 d after the operation was 23.0％(84/366).The incidence of device-related intraoperative complications was 3.6％(13/366).The median time from arterial puncture to recanalization was 75(52,110)min,and the median time from onset to recanalization was 370(280,488)min.(2)The good prognosis rates at 90 d after the operation in the anterior and posterior circulation occlusion groups were 55.1％(163/296)and 47.1％(33/70),respectively.The immediate successful recanalization rates were 93.2％(276/296)and 87.1％(61/70),respectively.The immediate complete recanalization rates were 79.1％(234/296)and 68.6％(48/70),respectively.The incidence of sICH within 24h after the operation was 12.2％(36/296)and 5.7％(4/70),respectively.The incidence of device-related intraoperative complications was 3.7％(11/296)and 2.9％(2/70),respectively.The all-cause mortality rate within 90 d after the operation was 21.6％(64/296)and 28.6％(20/70),respectively.There were no statistically significant differences between the two groups in the above aspects(all P＞0.05).Conclusions The application of the domestic RECO thrombectomy stent in the treatment of AIS caused by intracranial vessel occlusion can effectively and safely achieve vascular recanalization.The results of this study still need to be further verified by prospective controlled studies.

Aim To investigate the effect of Senecio scandens Buch.-Ham on inflammatory pain mediated by mast cell P2X7 receptor.Methods Using the ATP-induced foot inflammatory pain,immunofluores-cence and toluidine blue staining techniques were used to investigate whether Senecio scandens has inhibitory effect on P2X7 receptor on mast cells.Using the calci-um ion imaging experimental technology,to explore whether Senecio scandens inhibit the intracellular cal-cium ion enrichment caused by activation of P2X7 re-ceptor on mouse peritoneal mast cell.The whole-cell patch clamp technique was used to investigate whether senecio scandens could inhibit the inward current in-duced by activation of P2X7 receptor on mouse perito-neal mast cell.Results In vivo,Senecio scandens alle-viate ATP induced inflammatory pain(3.9 g·kg-1:P＜0.05),and significantly inhibited the infiltration of P2X7 receptor-positive mast cells(3.9 g·kg-1:P＜0.05).Knockout of mast cell can reduce the analgesic effect of Senecio scandens(3.9 g·kg-1:P=0.645).In vitro.The experiment results show that senecio scandens can significantly inhibit the calcium influx(300 mg·L-1:P＜0.05;1 g·L-1:P＜0.01;3 g·L-1:P＜0.01)and the inward current mediated by P2X7 receptor in mast cell(1 g·L-1:P＜0.01).Conclusion Senecio scandens alleviate inflammatory pain by inhibiting mast cell P2X7 receptor.

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.

Accurate prediction of drug responses in cancer cell lines (CCLs) and transferable prediction of clinical drug responses using CCLs are two major tasks in personalized medicine. Despite the rapid advancements in existing computational methods for preclinical and clinical cancer drug response (CDR) prediction, challenges remain regarding the generalization of new drugs that are unseen in the training set. Herein, we propose a multimodal fusion deep learning (DL) model called drug-target and single-cell language based CDR (DTLCDR) to predict preclinical and clinical CDRs. The model integrates chemical descriptors, molecular graph representations, predicted protein target profiles of drugs, and cell line expression profiles with general knowledge from single cells. Among these features, a well-trained drug-target interaction (DTI) prediction model is used to generate target profiles of drugs, and a pretrained single-cell language model is integrated to provide general genomic knowledge. Comparison experiments on the cell line drug sensitivity dataset demonstrated that DTLCDR exhibited improved generalizability and robustness in predicting unseen drugs compared with previous state-of-the-art baseline methods. Further ablation studies verified the effectiveness of each component of our model, highlighting the significant contribution of target information to generalizability. Subsequently, the ability of DTLCDR to predict novel molecules was validated through in vitro cell experiments, demonstrating its potential for real-world applications. Moreover, DTLCDR was transferred to the clinical datasets, demonstrating satisfactory performance in the clinical data, regardless of whether the drugs were included in the cell line dataset. Overall, our results suggest that the DTLCDR is a promising tool for personalized drug discovery.

Ganoderic acid is a class of lanostane-type triterpenoids found in Ganoderma species, and is one of the most important pharmacologically active components in G. lucidum, exhibiting antioxidant, anti-neuropsychiatric, anti-tumor, and immune-enhancing properties. The content of ganoderic acid in G. lucidum is very low, and the traditional extraction process is complex, yielding minimal amounts at high cost. The biosynthetic pathway of G. lucidum triterpenoids(GLTs), including the synthesis of different structural forms of ganoderic acid from lanosterol, as well as the molecular regulatory mechanisms involving key regulatory enzyme genes and their functions, are not yet fully understood. With the continuous development of synthetic biology technologies, there has been a deeper understanding of the biosynthesis and metabolic regulation pathways of ganoderic acid and its derivatives at the molecular level. Research has explored the key regulatory enzyme genes related to ganoderic acid biosynthesis and their functions. Moreover, through the optimization of synthetic biology and culture conditions, large-scale production and preparation of GLTs at the cellular level have been achieved. This paper reviews and analyzes the latest research progress on the biosynthesis pathways and metabolic regulation of GLTs, focusing on the configuration of ganoderic acid and its derivatives, the biosynthetic pathways, key enzyme genes, transcription factors related to ganoderic acid biosynthesis, signal transduction mechanisms, and factors affecting triterpenoid biotransformation. This review is expected to provide a theoretical basis and technical reference for improving the efficient production of triterpenoid pharmacological components and the exploitation and utilization of G. lucidum resources.
Triterpenes/chemistry* ; Reishi/chemistry* ; Biosynthetic Pathways ; Lanosterol