Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.

Objective:To evaluate the diagnostic performance of radiomics model based on contrast-enhanced ultrasound(CEUS) in predicting pathological complete response(pCR) after neoadjuvant chemoradiotherapy(nCRT) in patients with locally advanced rectal cancer(LARC).Methods:One hundred and six patients with LARC who underwent total mesorectal excision after nCRT between April 2018 and April 2023 in the First Affiliated Hospital of Guangxi Medical University were retrospectively included, the patients were randomly divided into a training set of 63(14 pCR patients) and a validation set of 43(12 pCR patients) in a 6∶4 ratios. Radiomics features were extracted from the tumors′ region of interest of CEUS images based on PyRadiomics. Intra-class correlation coefficient(ICC), Mann-Whitney U test, and least absolute shrinkage and selection operator(LASSO) algorithms were used to reduce features dimension. Finally, 7 radiomics features relevanted to pCR were selected to construct an ultrasomics model using elastic network regression, based on the R language. A combined model was constructed by jointing clinical feature. The performance of the models was assessed with the area under the ROC curve(AUC). Results:The AUC of the ultrasomics model and the combined model was 0.695(95% CI=0.532-0.859) and 0.726(95% CI=0.584-0.868) respectively in the training set. The AUC of the ultrasomics model and the combined model was 0.763(95% CI=0.625-0.902) and 0.790(95% CI=0.653-0.928) respectively in the validation set. Both univariate and multivariate Logistic regression analyses showed that CA199( P<0.05) and ultrasomics score( P<0.001) could be an independent predictor of pCR after nCRT in patients with LARC. Conclusions:The CEUS-based radiomics scores has certain predictive value for whether LARC patients achieve pCR after nCRT, and may provide a non-invasive imaging biomarker for predicting LARC patients achieve pCR after nCRT.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

To analyze the trends in disease burden and risk factors of depression among the elderly population in China from 1990 to 2021, and to provide a theoretical basis for the prevention, treatment, and policy-making of geriatric depression in China.

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

OBJECTIVE: The compatibility of Eucommia ulmoides (Eu) and Psoralea corylifolia (Pc) on the pharmacokinetic (PK) properties in the rat was explored in this study. METHODS: Eu extract, Pc extract and the combined extracts (crude drug ratio was 2:1) was administered by gavage, respectively. Two PK experiments were conducted. In first one, the blood samples were collected via the occuli chorioideae vein to get the PK properties of the components. In second one, the blood samples were simultaneously collected via the internal jugular vein or portal vein at different time points and the concentrations of target ingredients were detected by LC/MS/MS to clear the location where the interaction of Eu and Pc took place in vivo. RESULTS: Eight of 11 ingredients in Eu and Pc extract were determined in rat plasma. The exposure levels of geniposidic acid (GPA), aucubin (AU), geniposide (GP), pinoresinol diglucoside (PDG), psoralen glycosides (PLG) and isopsoralen glycosides (IPLG) were decreased 1/5-2/3 after administration of combined extracts. Comparing to the combined administration, the exposure of GPA and AU in plasma of single Eu administration collected via the portal vein were decreased 1/3-2/3, and the values of AUC_0-24h and AUC_0-∞ of GP collected from the portal vein or internal jugular vein were double increased. The other components' parameters were not significantly changed. CONCLUSION In summary, the Pc and Eu combined administration could affect the exposure of the main components of Eu extract in rats due to the changed intestinal absorption. The research on the compatibility of Pc and Eu was helpful to guide the clinical administration of Eu and Pc simultaneously.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.

Objective:To observe the effect of electroacupuncture(EA)combined with oriented conductive bio-protein hydrogel(OCBH)on the recovery of nerve function in rats with complete spinal cord injury(SCI)and to explore its effect and mechanism on the formation and changes of glial scars.Methods:A total of 72 female Sprague-Dawley rats were randomly divided into groups according to the treatment received.A rat model of complete SCI was constructed using a spinal cord transection.Behavioral assessments,hematoxylin-eosin(H&E)staining,immunofluorescence staining,and Western blotting were performed at a fixed period after the operation.Results:The material group and the material+EA group obtained better results in the behavioral as-sessments(all P＜.05)and the H&E staining.In the immunofluorescence staining and Western blotting,the GFAP protein was expressed more and denser in the material group and the material+EA group than in the model group,and the density of the GFAP expression in the material+EA group was lower at week 12 than in the material group(all P＜.05).The expression of complement C3 in the model,material,and material+EA groups decreased in turn.Some inflammatory factors and the NF-kB signaling pathway showed similar results in the Western blotting(all P＜.05).The expression of the GDNF protein in the material+EA group was significantly higher than that in the model group and the material group(both P＜.01).Conclusion:EA combined with OCBH can promote the recovery of motor functions after SCI by facili-tating the formation of glial scars in the early stage,preventing the further spread of an inflammatory response that would affect the activation of A1/A2 astrocytes and change the morphology of glial scars at the spinal cord-material interface in its late stage.

Objective:To construct a plan for relieving fatigue in breast cancer patients undergoing chemotherapy.Methods:We combined literature and clinical experience to construct a fatigue relief plan for breast cancer chemotherapy patients from August to October 2020. A total of 21 domestic two-glandular surgeons, nursing experts, and surgical nursing teachers were invited to conduct 2 rounds of Delphi expert letter inquiries, and analyzed the positive coefficient of experts and the degree of expert authority to evaluate the reliability of experts, and evaluated the coordination degree of expert opinions through the coefficient of variation and Kendall's harmony coefficient.Results:The effective response rate of the two rounds of questionnaires was 100%, the enthusiasm coefficient of experts was very high. The authority coefficients of the 2 rounds of consulting experts were 0.89 and 0.90 respectively (all>0.7), expert authority coefficient was very high. The Kendall harmony coefficients of the first-level and second-level indicators in the first round were 0.160 and 0.086, statistically significant (all P<0.05). In the second round, the Kendall′s harmony coefficients of dimension, first-level and second-level indicators were 0.190, 0.211, 0.378, statistically significant (all P<0.05). The coefficient of variation of each item in the second round was 0.04-0.12, and the full score rate was 28.57%-95.24%. All met the index screening standards established by the scheme. Finally, 3 dimensions, 3 first-level indicators and 16 third-level indicators were determined. Conclusions:The fatigue relief plan for breast cancer chemotherapy patients has necessity, practicality and scientificity.It has guiding significance for standardizing the fatigue relief of patients undergoing chemotherapy after radical mastectomy.

Objective:To explore the nursing effect of clinical nursing pathway in emergency care of severe pneumonia and its effect on lung function.Methods:A total of 90 patients with severe pneumonia in Lianyungang First People ′s Hospital of Jiangsu Province from June 2017 to July 2019 were selected as subjects. The randomized patients were divided into control group ( n=45 cases) and observation group ( n=45 cases). The control group received routine nursing. The observation group was combined with the clinical nursing pathway on the basis of the control group. Both groups were treated for 1 month. The symptom improvement time, lung function level and nursing satisfaction were compared. Results:The improvement time of wheezing (3.45 ± 1.06) d, the improvement time of antipyretic fever (3.48 ± 1.08) d, and the improvement time of lung rales (4.31 ± 0.49) d in the observation group were shorter than those in the control group [(7.01 ± 1.42) d, (4.56 ± 1.32) d, (6.62 ± 0.79) d] ( t value was 9.642, 7.375, 6.189, P <0.05); maximum voluntary minute ventilation (MVV) of the observation group in 1 month after nursing , Vital capacity (VC) and 1s forced expiratory volume (FEV1) levels were higher than before nursing ( P <0.05); MVV (71.42 ± 18.75) L, VC (72.41 ± 17.74)% and FEV1 were observed in the observation group 1 month after nursing (67.36 ± 18.48) L, all higher than (62.38 ± 16.69) L, (60.18 ± 15.69)% and (59.15 ± 17.13) L of the control group ( t value was 6.393, 5.544, 7.491, P <0.05); observation group after-care, nursing method, content, form of nursing, nursing service attitude, and nursing effect satisfaction were 97.78% (44/45), 95.56% (43/45), 97.78% (44/45), 93.33% (42/45 ), 95.56% (43/45), which were higher than 80.00% (36/45), 90.48% (38/45), 82.22% (37/45), 77.78% (35/45), 80.00% of the control group (36/45), with statistically significance ( χ2 value was 5.412-9.581, P <0.05). Conclusions:The clinical nursing pathway is effective for emergency nursing of patients with severe pneumonia. It can shorten the time of symptom disappearance, improve the lung function level and satisfaction of nursing, and it is worthy of popularization and application.