This study systematically examined the effects of atomization as a transdermal permeation enhancer on the transdermal delivery of active ingredients with different physicochemical properties and investigated the underlying mechanisms. Porcine ear skin served as an in vitro model, and skin permeation experiments were conducted using Franz diffusion cells. Receptor fluids were collected at specific time points, and samples of the stratum corneum and viable epidermis–dermis were separated and prepared. Quantitative and visualization methods, including high-performance liquid chromatography, fluorescence derivatization, and confocal laser scanning microscopy, were used to compare skin retention and transdermal permeation of adenosine (AD), tranexamic acid (TXA), calcein (CAL), and tocopheryl acetate (TA) under atomized and non-atomized conditions. Additionally, transepidermal water loss (TEWL) measurements and attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) were employed to analyze the mechanism behind the penetration enhancement caused by atomization. The findings showed that atomization increased skin retention within the stratum corneum and viable epidermis–dermis, as well as the transdermal permeation of all four active ingredients to varying degrees. The most significant enhancement was observed for TXA, which has a relatively low molecular weight and moderate lipophilicity, while the enhancement effects for highly hydrophilic AD and highly lipophilic TA were comparatively limited; however, atomization significantly increased the skin retention of TA. TEWL results indicated that skin permeability increased within 4 hours after atomization and largely recovered within 8 hours. ATR-FTIR analysis suggested that atomization may facilitate transdermal delivery by disrupting the lipid order and keratin conformation in the stratum corneum.This study provides theoretical support and experimental references for the advancement of atomization transdermal delivery technology, as well as the design and development of related atomization products.

OBJECTIVE To analyze the characteristics of peripheral blood leukocyte morphology,scatterplot and leukocyte cell population data(CPD)in patients with severe fever and thrombocytopenia syndrome(SFTS),infec-tious mononucleosis(IM)and hemorrhagic fever with renal syndrome(HFRS),and to explore their differences.METHODS Blood routine examination data were collected,including microscopic cell images,scatter-plots and leukocyte CPD study parameters from 44 patients diagnosed with SFTS,17 with IM and 11 with HFRS at the First Affiliated Hospital with Nanjing Medical University from Mar.2023 to May 2024.These data were compared with those of healthy controls to explore specific differences in the characteristics of peripheral blood leu-kocyte.RESULTS All 3 viral infections exhibited a left shift in the nucleus under the microscope,yet the blood routine scatterplot and microscopic leukocyte characteristics differed.SFTS commonly presented with a plasmacy-toid reactive lymphocyte with scattered points appearing in the upper reactive lymphocyte area of the scatterplot.IM showed a predominant irregular fried-egg-like reactive lymphocyte under the microscope,with the scatterplot typically presenting a rocket-like shape,in patients with HFRS,there was a significant increase in im-mature granulocytes in peripheral blood and plasmacytoid reactive lymphocyte scatter points with blue immature granulocyte scatter points visible.The fluorescence distribution width(MO-WY)of monocytes in the SFTS group was lower than those in the IM,HFRS and healthy control groups(P＜0.05).Compared to SFTS,IM and healthy control groups,the lateral scattered light distribution width(NE-WX)and fluorescence distribution width(NE-WY)of neutrophils in the HFRS group were both increased(P＜0.05).CONCLUSIONS There are signifi-cant differences in the characteristics of peripheral blood leukocyte morphology,scatterplot and CPD study param-eters among three viral infection diseases SFTS,IM and HFRS.These differences can provide early clinical advice and assist in clinical differentiation.

Objective:To investigate the impact of internationalization at home medical education on clinical medical undergraduate abilities based on value-added assessment, and to provide a reference for deepening education and teaching reform in medical colleges and universities.Methods:The study subjects consisted of undergraduate students enrolled in 2020 at Chongqing Medical University majoring in clinical medicine (five-year program) and clinical medicine (Sino-foreign cooperative education program). The questionnaire in the 2023 China Medical Students Survey, initiated by the National Medical Education Development Center, was used in this study. SPSS 27.0 was used for independent samples t-test and hierarchical linear regression. Results:Compared with the control group, the clinical medical undergraduates who received internationalization at home medical education had higher scores in academic article writing ability [(3.89±0.73) vs. (2.87±0.80)], literature retrieval and information management ability [(3.98±0.64) vs. (3.43±0.65)], and international communication and global health concept [(3.81±0.68) vs. (3.52±0.69)]. Controlling for individual-level student variables, internationalization at home medical education had a positive effect on clinical medicine undergraduate abilities based on value-added assessment ( β=5.003, P<0.001). Conclusions:The internationalization at home medical education in Chongqing Medical University enhances the abilities of clinical medical undergraduates, and provides a reference for the comprehensive improvement of the education quality of medical talents.

Objective:To evaluate the feasibility and outcomes of transnasal endoscopic clipping of the paraclival internal carotid artery (ICA) in skull base surgery.Methods:The paraclival ICA was anatomically dissected in cadaveric head specimens. The clinical data of 15 patients with skull base lesions involving the ICA who admitted to the Department of Otorhinolaryngology Head and Neck Surgery at Tianjin Huanhu Hospital from January 2021 to December 2023 were retrospectively analyzed. Among them, 4 patients underwent transnasal endoscopic clipping of the paraclival ICA and concurrent lesion resection. The surgical methods were summarized, and the key points and indications of this technique were analyzed.Results:Intraoperative clipping of the ICA was successful and hemostatic in all 4 patients. Postoperatively, 3 patients had no complications, while 1 patient developed delayed ischemic cerebral infarction. Two patients were cured, 1 patient was maintained on immunotherapy, and 1 patient died. During follow-up, the clip was in situ in 1 patient, had detached in another, and was obscured by temporal muscle coverage in the remaining 2 patients.Conclusions:Transnasal endoscopic clipping of the paraclival ICA represents a potential option for managing the ICA in skull base surgery. However, it carries significant risks and limitations, mandating careful patient selection based on specific circumstances.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

OBJECTIVE To analyze the characteristics of peripheral blood leukocyte morphology,scatterplot and leukocyte cell population data(CPD)in patients with severe fever and thrombocytopenia syndrome(SFTS),infec-tious mononucleosis(IM)and hemorrhagic fever with renal syndrome(HFRS),and to explore their differences.METHODS Blood routine examination data were collected,including microscopic cell images,scatter-plots and leukocyte CPD study parameters from 44 patients diagnosed with SFTS,17 with IM and 11 with HFRS at the First Affiliated Hospital with Nanjing Medical University from Mar.2023 to May 2024.These data were compared with those of healthy controls to explore specific differences in the characteristics of peripheral blood leu-kocyte.RESULTS All 3 viral infections exhibited a left shift in the nucleus under the microscope,yet the blood routine scatterplot and microscopic leukocyte characteristics differed.SFTS commonly presented with a plasmacy-toid reactive lymphocyte with scattered points appearing in the upper reactive lymphocyte area of the scatterplot.IM showed a predominant irregular fried-egg-like reactive lymphocyte under the microscope,with the scatterplot typically presenting a rocket-like shape,in patients with HFRS,there was a significant increase in im-mature granulocytes in peripheral blood and plasmacytoid reactive lymphocyte scatter points with blue immature granulocyte scatter points visible.The fluorescence distribution width(MO-WY)of monocytes in the SFTS group was lower than those in the IM,HFRS and healthy control groups(P＜0.05).Compared to SFTS,IM and healthy control groups,the lateral scattered light distribution width(NE-WX)and fluorescence distribution width(NE-WY)of neutrophils in the HFRS group were both increased(P＜0.05).CONCLUSIONS There are signifi-cant differences in the characteristics of peripheral blood leukocyte morphology,scatterplot and CPD study param-eters among three viral infection diseases SFTS,IM and HFRS.These differences can provide early clinical advice and assist in clinical differentiation.

There is significant inter-individual variation of pharmacokinetics and pharmacody-namics in patients receiving tacrolimus(TAC)for an-ti-rejection therapy,which cause the rejection or toxic action.Based on results of therapeutic drug monitoring and pathophysiological index of trans-plant patients,the individualized dosing regimen can be designed and adjusted by using model in-formed precision dosing(MIPD).The patients'clini-cal outcome can be improved.In the consensus,the different methods of MIPD used for patients re-ceived TAC for anti-rejection therapy were intro-duced,which can be used for the designing and ad-justing doing regimen,predicting adverse drug reac-tion,improving medication adherence and econom-ics during therapy.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.