Objective To prepare a dissolvable microneedle(MN)patch loaded with sodium houttuyfonate(SH)combined with erythromycin(ERY)(SH+ERY-MN patch),to characterize its properties,and to investigate its synergistic anti-acne effects and the mechanisms involved.Methods The SH+ERY-MN patch was prepared by two-step centrifugation.The morphology and skin puncture performance of the microneedles were evaluated using scanning electron microscopy,puncture tests,and other methods.The combined antibacterial effect was assessed using the checkerboard assay.The in vitro anti-inflammatory effect of the SH+ERY-MN patch was evaluated by quantitative PCR(qPCR)and enzyme-linked immunosorbent assay(ELISA).The therapeutic effect of the SH+ERY-MN patch on acnes in mice was investigated using an animal model.Results The microneedle patch prepared in the study had well-aligned microneedles,excellent needle shape,and good mechanical properties,which could effectively penetrate the skin to reach the superficial dermis.The minimum inhibitory concentration(MIC)of ERY against acne was 1.28 mg/mL.When ERY was combined with SH,the results showed that the fractional inhibitory concentration(FIC)was 0.375,indicating that the medication combination had a synergistic antibacterial effect.In particular,the MIC value of ERY in combination was 1/4 of that of ERY used alone.The results of in vitro qPCR showed that SH+ERY-MN could downregulate the production of interleukin(IL)-1β,IL-18,tumor necrosis factor α(TNF-α),inhibitor of κB(I-κB),Toll-like receptor 4(TLR4),NLR family pyrin domain containing 3(NLRP3),and cysteine-aspartic proteases(Caspase-1)induced by Propionibacterium acnes(PA)in cell culture supernatant(P＜0.05).According to the in vivo findings,SH+ERY-MN had a significant anti-acne effect and effectively alleviated cytokine-mediated inflammatory responses.The results of qPCR and ELISA showed that SH+ERY-MN could effectively reduce the levels of IL-1β,IL-18,NLRP3,and Caspase-1 in the serum of the mouse acne inflammation model(P＜0.01),and had good antibacterial and anti-inflammatory effects.Conclusion SH+ERY-MN patch was successfully prepared and demonstrated obvious anti-acne effects.The SH+ERY-MN patch enhances the transdermal delivery of SH combined with ERY.It provides an innovative method for acne treatment and creates new possibilities for achieving effective drug delivery and improving therapeutic efficacy.

Objective To investigate the effects of early statin therapy on collateral circulation,responsible vessel improvement,and thromboxane B2(TXB2)/prostaglandin F1(PGF1α)in acute ischemic stroke with large vessel occlusion(AIS-LVO).Methods From May 2021 to May 2023,105 AIS-LVO patients treated with statins within 3 days of admission were selected as the statin group from the Neurology Department of Taiyuan Iron and Steel(Group)General Hospital.Concurrently,105 early AIS-LVO patients not treated with statins were selected as the non-statin group.The study compared symptom scores[National Institutes of Health Stroke Scale(NIHSS),modified Rankin Scale(mRS),Swallowing Standard Assessment(SSA),and Functional Oral Intake Scale(FOIS)scores],responsible vessel improvement,TXB2/PGF1α levels,and endothelial function indicators[basic fibroblast growth factor(bFGF)and circulating endothelial cells(CECs)].Results Af-ter 1 and 2 weeks,the statin group showed lower NIHSS,mRS,and SSA scores,and higher FOIS scores compared to the non-statin group(P<0.02).The statin group demonstrated higher rates of responsible vessel velocity increase,collateral circulation compensation,and superior CTA collateral circulation grading(P<0.05).At 1 and 2 weeks,the statin group had lower TXB2 and TXB2/PGF1α levels,and higher PGF1α levels compared to the non-statin group(P<0.02).The statin group showed lower bFGF levels and higher CECs levels(P<0.02).After 3 months,the statin group had a higher proportion of mRS scores of 0～2(P<0.05).Conclusion Early statin therapy in AIS-LVO patients can improve responsible vessel blood flow and endothelial function,regulate TXB2/PGF1α levels,promote collateral circulation compensation,and enhance swallowing and neurological function recovery.

Objective To construct a graded nursing program for exercise rehabilitation of children with hematopoietic stem cell transplantation(HSCT)and carry out a preliminary application,aiming to provide a basis for healthcare personnel to guide the exercise rehabilitation of children with HSCT.Methods Literature analysis and Delphi expert correspondence were used to construct a graded nursing program of exercise rehabilitation for children with HSCT.Through the convenience sampling method,children with HSCT in the hematology department of a tertiary-level children's hospital in Suzhou City were selected as the study subjects from June-December 2023,of which 26 children with HSCT from September-December 2023 served as an experimental group,and 23 children with HSCT from June-August 2023 as a control group.The experimental group was applied with the graded nursing program of exercise rehabilitation,and the control group was applied with the conventional nursing care.The comparison of cardiorespiratory fitness and adverse events between the 2 groups after 8 weeks of exercise intervention was conducted,and the adherence to the exercise intervention programme in the experimental group was recorded.Results The final constructed graded care program of exercise rehabilitation for children with HSCT included 6 primary indicators,20 secondary indicators,and 44 tertiary indicators.Finally,21 children in the experimental group and 23 children in the control group were included in the study.After the intervention,the 6 min walking distance of the experimental group increased compared with that of the control group,and the difference was statistically significant(P＜0.001).85.71％of children in the experimental group had good exercise compliance,and there was no adverse events in both groups.Conclusion The constructed graded nursing program of exercise rehabilitation for children with HSCT is scientific,reasonable,safe and feasible,which can improve the cardiorespiratory capacity of children with HSCT and provide the basis for their exercise rehabilitation.

Objective To investigate the expression of serum microRNA-204-5p(miR-204-5p)in patients with sudden deafness(SD)and its relationship with cochlear function and hearing prognosis.Methods A to-tal of 113 SD patients admitted to this hospital from October 2020 to October 2023 were selected as the case group.According to the hearing prognosis of SD patients,they were divided into a poor prognosis group(n=43)and a good prognosis group(n=70).Another 95 healthy people who underwent the physical examination were selected as the control group.Real-time fluorescent quantitative PCR and enzyme-linked immunosorbent assay were used to detect serum levels of miR-204-5p and endothelin-1(ET-1),and the relationship between them and cochlear function was analyzed.Automatic hemorheology instrument was used to detect the hemo-dynamic parameters.Multivariate Logistic regression was used to analyze the influencing factors of hearing prognosis in SD patients.Receiver operating characteristic(ROC)curve was used to analyze the predictive val-ue of serum miR-204-5p in hearing prognosis of SD patients.Results The serum levels of miR-204-5p and ET-1 and hemodynamic parameters including plasma viscosity(PV),low-shear viscosity(LSV)and whole blood high-shear viscosity(HSV)in the case group were significantly higher than those in the control group(P<0.05).The incidence of cochlear dysfunction in the miR-204-5p high expression group was higher than that in the miR-204-5p low expression group(P<0.05).The levels of serum miR-204-5p,ET-1,PTA,HSV,LSV and PV in the poor prognosis group were significantly higher than those in the good prognosis group(P<0.05).HSV,LSV,PV,miR-204-5p and ET-1 were related factors affecting the hearing prognosis of SD patients(P<0.05).The area under the curve of serum miR-204-5p,ET-1 combined with hemodynamic pa-rameters to predict the hearing prognosis of SD patients was 0.976.It was better than that of each individual diagnosis(Zfive combination-HSV=3.464,Zfive combination-LSV=3.014,Zfive combination-PV=3.741,Zfive combination-miR-204-5p=3.476,Zfive combination-ET-1=2.829,P=0.001,0.003,<0.001,0.001,0.005).The sensitivity and specificity of combined prediction were 95.35%and 88.57%,respectively.Conclusion Serum miR-204-5p level is significantly in-creased in SD patients,which is closely related to cochlear function and hearing prognosis.Serum miR-204-5p and ET-1 levels combined with hemodynamic indicators have higher predictive efficiency for hearing prognosis in SD patients.

ObjectiveTo explore psychological experiences and care needs of elderly patients with chronic obstructive pulmonary disease (COPD) following dysphagia. MethodsFrom April to June, 2024, 13 elderly patients with COPD and dysphagia received treatment in Yixing No. 2 People's Hospital (Yixing Occupational Disease Institute) and Northern Jiangsu People's Hospital were interviewed. Nvivo 11.0 and content analysis were employed to analyze and summarize themes. ResultsTwo main themes were identified. The psychological experiences included fear of eating due to swallowing and choking, swallowing anxiety in social situations, concerns about malnutrition, and emotional loss related to family. The care needs included improvement in swallowing function, adjustment of food texture, assistance with disease adaptation and effective access to health education information. ConclusionHealthcare professionals should thoroughly understand the psychological and needs of elderly patients with COPD-related dysphagia, and comprehensive nursing strategies should be developed and implemented to improve swallowing function and overall quality of life.

ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time， quasi-molecular ion peaks， secondary fragmentation ions， and literature reports， and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract， the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds， including 21 phenolic acids， 23 diterpenes， 6 flavonoids， 7 organic acids， 3 volatile oils and 13 others， were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma， the major metabolic pathways included reduction， hydration， hydroxylation， demethylation， methylation， sulfation and others， these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones， which may be the material basis of the efficacy. This study can provide reference for pharmacological research， quality control， and clinical application of Danshenyin.

ObjectiveTo establish fingerprint profiles and a quantitative determination method for Lycii Cortex， providing a scientific basis for the formulation of quality standards for Lycii Cortex and its roasted products. MethodsHigh performance liquid chromatography（HPLC） was developed for the quantitative method for determining kukoamine B in Lycii Cortex and its roasted products on an Alphasil XD-C₁₈ CH column（4.6 mm×250 mm， 5 μm）. HPLC fingerprint profiles were established for 10 batches of Lycii Cortex and its roasted products， and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the common peaks based on reference standards， literature and MS information. Quality evaluation indicators included yield of decoction pieces， appearance properties， content of kukoamine B， and fingerprint profiles. The temperature and time of the roasting process were investigated to select the optimal preparation process， which was then verified. Additionally， chemical pattern recognition was combined to assess the differences in the chemical composition of Lycii Cortex before and after roasting， as well as among samples from different origins. ResultsQuantitative analysis indicated that the contents of kukoamine B in Lycii Cortex and its roasted products were 0.35%-5.51% and 0.24%-4.15%， respectively. The transfer rate of kukoamine B was 58.6%-78.9% after roasting. The fingerprint profile analysis demonstrated that the method established in this study effectively separated kukoamine B from other components in the samples and distinctly differentiated it from its impurity peak， cis-N-caffeoylputrescine. The HPLC fingerprint profiles of Lycii Cortex and its roasted products showed high similarity（all above 0.95）， with 7 common peaks identified and five common components， including kukoamine B， cis-N-caffeoylputrescine， N-coumaroyl tyramine， feruloyltyramine， and glucosyringic acid， confirmed. Process optimization confirmed that baking at 110 ℃ for 20 min was a stable and feasible method for roasting Lycii Cortex. Principal component analysis and cluster analysis showed that there was little difference in the chemical composition between raw and roasted Lycii Cortex， but the quality of Lycii Cortex from different origins differed greatly. ConclusionThis study successfully established the fingerprint profiles and a quantitative method for the effective component kukoamine B in Lycii Cortex and roasted Lycii Cortex. The qualitative and quantitative analyses clarified that the impact of the roasting process on the chemical composition of Lycii Cortex was less significant than the variations due to its geographical origin. The findings of this study offer a reference for the development of quality evaluation methods and the establishment of quality standards for Lycii Cortex and its processed products.

Computational analysis can accurately detect drug-gene interactions(DGIs)cost-effectively.However,transductive learning models are the hotspot to reveal the promising performance for unknown DGIs(both drugs and genes are present in the training model),without special attention to the unseen DGIs(both drugs and genes are absent in the training model).In view of this,this study,for the first time,proposed an inductive learning-based model for the precise identification of unseen DGIs.In our study,by integrating disease nodes to avoid data sparsity,a multi-relational drug-disease-gene(DDG)graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions.Following the extraction of graph features by utilizing graph embedding algorithms,our next step was the retrieval of the attributes of individual gene and drug nodes.In this way,a hybrid feature charac-terization was represented by integrating graph features and node attributes.Machine learning(ML)models were built,enabling the fulfillment of transductive predictions of unknown DGIs.To realize inductive learning,this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights,enabling inductive predictions for the unseen DGIs.Consequently,the final model was superior to existing models,with significant improvement in predicting both external unknown and unseen DGIs.The practical feasibility of our model was further confirmed through case study and molecular docking.In summary,this study establishes an efficient data-driven approach through the proposed modeling,suggesting its value as a promising tool for accelerating drug discovery and repurposing.

Objective To investigate the therapeutic mechanism of Danzhi Jiangtang Capsule(DZJTC)for repairing renal vascular endothelial injury in rats with diabetic nephropathy(DN).Methods Fifty male SD rat models of DN,established by left nephrectomy,high-sugar and high-fat diet and streptozotocin injection,were randomized into DN model group,low-,medium-,and high-dose DZJTC treatment groups,and DAPT(a γ-secretase inhibitor)treatment group,with 10 rats with normal feeding as the control group.DZJTC was administered by daily gavage at 0.315,0.63,or 1.26 g/kg,and DAPT(20 mg/kg,dissolved in 50%CMC-Na solution)was given by gavage every other day for 4 weeks;normal saline was given in the control and model groups.After treatment,the levels of creatinine(CRE),blood urea nitrogen(BUN),and microalbuminuria(mALB)were detected with ELISA,and renal pathologies were observed by transmission electron microscopy.Renal expressions of vascular endothelial growth factor(VEGF)and endothelin-1(ET-1)were measured by immunohistochemistry,and the protein expressions of CD31 and Notch signaling pathway components were detected using Western blotting.Results The rat models of DN showed significantly increased CRE,BUN,and mALB levels,obvious renal pathologies under electron microscopy,increased renal VEGF,ET-1 and CD31 expressions,and upregulated Notch1,NICD,and MAML1 protein levels.Treatment with DZJTC at the 3 doses and DAPT significantly reduced CRE,BUN,and mALB levels,improved renal pathology,decreased VEGF,ET-1 and CD31 expressions,and lowered Notch1,NICD and MAML1 levels,and the effects were the most pronounced with high-dose DZJTC.Conclusion DZJTC ameliorates hyperproliferation and dysfunction of renal vascular endothelium in DN rats possibly by regulating renal VEGF and ET-1 levels via inhibiting NICD-and MAML1-mediated Notch signaling pathway.

Objective:To analyze the clinical features and genetic sequencing results of a patient with Kallmann syndrome(KS) carrying digenic mutations who initially presented with osteoporosis, and to enhance awareness of this disease phenotype.Methods:Clinical data were collected, and peripheral blood DNA was extracted for whole-exome sequencing. Relevant literature was reviewed to summarize phenotypes associated with digenic/oligogenic variants involving CHD7.Results:The patient exhibited back pain, delayed development of secondary sexual characteristics, and hyposmia. Laboratory tests revealed reduced sex hormones and gonadotropin levels, while pituitary imaging was unremarkable. Bone mineral density imaging confirmed osteoporosis, and thoracolumbar X-rays showed multiple vertebral compression fractures. Genetic analysis identified a heterozygous splice-site mutation in CHD7(c.2698-1G>T) and a heterozygous missense mutation in WDR11(c.439G>A: p.D147N). According to ACMG criteria, the CHD7 mutation was classified as pathogenic, while the WDR11 variant was defined as a variant of uncertain significance(VUS). Literature review indicated that 40% of KS patients with digenic/oligogenic variants involving CHD7 presented with hearing or ocular abnormalities.Conclusion:This study reports a novel CHD7 mutation and a previously undescribed digenic combination of CHD7 and WDR11 variants in a KS patient. CHD7 variants may be implicated in auditory or ocular involvement in KS cases with digenic/oligogenic inheritances. KS patients may also manifest skeletal abnormalities in addition to hypogonadotropic hypogonadism. Tailored management of sex hormones and osteoporosis therapies across life stages is essential for optimizing bone health in KS.