OBJECTIVE To prepare the β -cyclodextrin （ β -CD） inclusion complex with volatile oil from Qianghuo qushi qingwen granules， and to characterize and quantitatively analyze the inclusion complex. METHODS The comprehensive scores calculated by inclusion rate and inclusion compound yield were used as indicators for screening the inclusion method. The single-factor experiments and Box-Behnken response surface experiments were used to op timize the inclusion conditions， with the above comprehensive score as response value， and taking the ratio of β -CD to volatile oil， inclusion temperature and inclusion time as indexes. The volatile oil inclusion complex of Qianghuo qushi qingwen granules was prepared according to the determined optimal process， followed by validation. Ultraviolet （UV）-visible spectroscopy， thin-layer chromatography （TLC）， and microscopic imaging were also performed. Ultra-high performance liquid chromatography was used to determine the contents of perillaldehyde， pogostone and atractylodin. RESULTS The saturation aqueous solution method was adopted. The optimal inclusion process conditions were as follows： the ratio of β -CD to volatile oil was 7.5∶1， the inclusion temperature was 40 ℃， and the inclusion time was 2.2 h. In three verification experiments， the average inclusion rate was 72.32%， the average yield of inclusion compound was 74.45%， the average comprehensive score was 72.96 points， and the relative error with the predicted value （74.15 points） of the model was 1.61%. UV-visible spectroscopy， TLC and microscopic imaging showed that β -CD and volatile oil successfully formed a new inclusion complex. The average contents of perillaldehyde， pogostone and atractylodin were 4.498 2， 0.814 9， 0.905 7 mg/g， respectively， with RSDs of 0.31%， 0.56% and 0.63% （ n ＝3）. CONCLUSIONS A stable and feasible preparation process of the volatile oil inclusion complex of Qianghuo qushi qingwen granules is successfully established.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

ObjectiveTo analyze and validate how Jiawei Sanpian decoction treats migraines by integrating network pharmacology, molecular docking technology, and experimental studies.MethodUsing network pharmacology, the chemical components and core target proteins of the Jiawei Sanpian decoction were analyzed. Key chemical components were docked with core targets using molecular docking, and the results were visualized. Nitroglycerin was injected into the dorsal cervical region to establish a rat migraine model. Finally, experiments were conducted to verify the effects of Jiawei Sanpian on related pathways and targets.ResultsFour notable chemical components were identified, namely, β-sitosterol, quercetin, mairin, and kaempferol. Five representative targets were identified, namely, insulin-like growth factor 1 (IGF-1), matrix metallopeptidase 2 (MMP-2), interleukin-2 (IL-2), superoxide dismutase 2 (SOD2), and inducible nitric oxide synthase (NOS2). Molecular docking results revealed that the minimum binding energies between the four chemical components and the five targets were below −5 kcal/mol, indicating favorable binding activity. Enzyme linked immunosorbent assay (ELISA) results demonstrated the efficacy of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1, IL-2, MMP-2, and SOD2 (P .001). Real-time quantitative polymerase chain reaction (RT-qPCR) results demonstrated the effectiveness of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1, IL-2, MMP-2, and SOD2 (P .001). After using erastin, the therapeutic effect of Jiawei Sanpian decoction declined.ConclusionThis study provides initial insights into the complex and multilayered therapeutic mechanisms of Jiawei Sanpian decoction in treating migraine, primarily through its diverse components, targets, and pathways. These findings indicate that Jiawei Sanpian decoction may exert its effects mainly through processes linked to the mitochondrial inflammatory pathway, thereby providing therapeutic benefits for migraine.

This study investigated the association between serum 25(OH)D 3 levels and cardiovascular risk-related indicators. 4 727 participants aged 20 and above from the National Health and Nutrition Examination Survey 2015-2018 database were enrolled. Body mass index, hypersensitive C-reactive protein, high density lipoprotein cholesterol, systolic blood pressure, waist-height ratio, and total cholesterol were selected as the research indicators. Weighted multiple linear regression models, subgroup analyses, smooth curve fitting, and saturation threshold effect analyses were employed to explore the relationship between serum 25(OH)D 3 and these indicators. The results showed that after full adjustment for covariates, every 1 nmol/L increase in serum 25(OH)D 3, the changes in β (95% CI) values for body mass index(BMI), hypersensitive C-reactive protein(hs-CRP), systolic blood pressure(SBP), waist-height ratio(WHtR), high density lipoprotein cholesterol(HDL-C), and total cholesterol(TC) were -0.05 (-0.06, -0.04) kg/m 2, -0.01 (-0.02, -0.01) mg/L, -0.02 (-0.04, -0.01) mmHg, -0.000 7 (-0.000 8, -0.000 6), 0.10 (0.08, 0.11) mg/dl, and 0.08 (0.04, 0.12) mg/dl, respectively. Female participants were more sensitive to changes in serum 25(OH)D 3, while participants aged 60 and above were relatively less sensitive. The relationship between serum 25(OH)D 3 and these indicators partially exhibited nonlinear patterns across different gender and age subgroups. The saturation threshold effect analysis revealed 8 meaningful inflection points. In summary, vitamin D has a close association with cardiovascular risk-related indicators.

Objective:To establish an animal model of trans-sutural distraction osteogenesis in SD rats.Methods:A self-designed V-shaped distraction device(distractor)was fabricated with the traction force(N)of 0,1.3,2.2,3.0,4.3 and 5.0 corresponding to the distraction length(mm)of 5,4,3,2,1 and 0 respectively,meeting the trans-sutural distraction osteogenesis requirements in skull of 5-week-old SD rats.The distractor was plased into the sagittal suture of 12 SD rats.Continuous sampling was conducted 1,3,5 and 7 days respectively(n=3)after operation.The tissue changes in the trans-sutural distraction area were observed by HE and Masson's trichrome staining.Inflammation levels were determined using Arg-1 immunofluorescence staining.The early angiogenesis was clarified through co-staining with CD31 and EMCN.Results:A stable trans-sutural distraction osteogenesis model was estab-lished,5 mm distraction osteogenesis width was observed completely within 7 days of distraction.Significant new bone formation was observed at 7 days after operation.Arg-1 expression increased and was concentrated at the bone margins,overlapping with the areas of new bone formation.EMCN expression gradually decreased,and by day 7 CD31 was predominant,indicating the basic maturation of blood vessels.Conclusion:This study successfully constructed a stable and effective trans-sutural distraction osteogenesis animal model,and provides an experimental basis for the investigation of its early continuous histological changes.

This study investigated the association between serum 25(OH)D 3 levels and cardiovascular risk-related indicators. 4 727 participants aged 20 and above from the National Health and Nutrition Examination Survey 2015-2018 database were enrolled. Body mass index, hypersensitive C-reactive protein, high density lipoprotein cholesterol, systolic blood pressure, waist-height ratio, and total cholesterol were selected as the research indicators. Weighted multiple linear regression models, subgroup analyses, smooth curve fitting, and saturation threshold effect analyses were employed to explore the relationship between serum 25(OH)D 3 and these indicators. The results showed that after full adjustment for covariates, every 1 nmol/L increase in serum 25(OH)D 3, the changes in β (95% CI) values for body mass index(BMI), hypersensitive C-reactive protein(hs-CRP), systolic blood pressure(SBP), waist-height ratio(WHtR), high density lipoprotein cholesterol(HDL-C), and total cholesterol(TC) were -0.05 (-0.06, -0.04) kg/m 2, -0.01 (-0.02, -0.01) mg/L, -0.02 (-0.04, -0.01) mmHg, -0.000 7 (-0.000 8, -0.000 6), 0.10 (0.08, 0.11) mg/dl, and 0.08 (0.04, 0.12) mg/dl, respectively. Female participants were more sensitive to changes in serum 25(OH)D 3, while participants aged 60 and above were relatively less sensitive. The relationship between serum 25(OH)D 3 and these indicators partially exhibited nonlinear patterns across different gender and age subgroups. The saturation threshold effect analysis revealed 8 meaningful inflection points. In summary, vitamin D has a close association with cardiovascular risk-related indicators.

Objective To study the role of curcumin-mediated sonodynamic therapy in the treatment of malignant melanoma,and to provide a new strategy for the treatment of malignant melanoma.Methods The ultrasonic sound and vibration method was applied to coat curcumin with mouse melanoma cell membrane,thereby forming biomimetic curcumin.The morphology of biomimetic curcumin was observed by transmission electron microscope.Flow cytometry was used to analyze the effect of biomimetic curcumin in terms of in vitro targeting,apoptosis,and intracellular reactive oxygen species(ROS)production.The in vivo experiment was divided into control group,US group,turmeric group,imitation turmeric group,and imitation turmeric+US group,with 3 mice in each group.The in vivo safety of biomimetic curcumin was evaluated by HE staining.In addition,HE,CD31,Ki67,and TUNEL stainings were performed to evaluate the in vivo anti-melanoma therapeutic effect of ultrasound combined with biomimetic curcumin.Results The biomimetic curcumin had a generally uniform morphology and possessed a core-shell structure.Flow cytometry analysis performed with FlowJo showed that the biomimetic curcumin could be effectively taken up by melanoma cells.The apoptosis rate was(10.30±0.61)％in the control group,(10.41±3.13)％in the ultrasound group,(24.97±1.38)％in the curcumin group,(31.39±3.84)％in the biomimetic curcumin group,and(40.89±0.79)％in the biomimetic curcumin and ultrasound combination group.The apoptosis rate in the biomimetic curcumin and ultrasound combination group was higher than those in the other groups(P＜0.05).The results of ROS flow cytometry showed that,compared with the control group,the ultrasound group demonstrated almost no increase in the fluorescence intensity,while the other groups showed an increase in the fluorescence intensity to varying degrees.There was no significant difference in the fluorescence intensity between the biomimetic curcumin group([1.10±0.38]％)and the curcumin group([0.73±0.26]％)(P＞0.05).The fluorescence intensity of the biomimetic curcumin and ultrasound combination group([3.35±0.04]％)was higher than those of the other groups(P＜0.05).HE staining showed no obvious abnormalities in the morphology of heart,liver,spleen,lung,and kidney tissues in any of the treatment groups.HE staining showed the most significant changes in cell morphology in the biomimetic curcumin and ultrasound combination group,followed by the biomimetic curcumin group and the curcumin group.No obvious abnormalities in tumor cell morphology were observed in the ultrasound group.According to the respective results of CD31 staining,Ki67 staining,and TUNEL staining,the biomimetic curcumin and ultrasound combination group had the largest brown area,the highest number of red fluorescence,and the highest number of green fluorescence,followed by the biomimetic curcumin group and the curcumin group.Conclusion The biomimetic curcumin displays uniform morphology,a core-shell structure,and good targeting properties.When it is used in combination with ultrasound,biomimetic curcumin demonstrates a good anti-tumor therapeutic effect both in vivo and in vitro.

Objective:To investigate the effect of the transcriptional coactivator Mediator 1 (Med1) on mouse hair regeneration, and to explore potential mechanisms.Methods:Med1 flox/flox C57BL/6J mice were mated with K14-Cre mice, and the mice with epidermis-specific knockout of Med1 gene, namely K14-Cre-expressing Med1 flox/flox mice (knockout group) , were obtained by using the Cre-Loxp system, while Med1 flox/flox mice without K14-Cre expression served as control group. Mice in the two groups (3 mice in each group) were raised together for 8 weeks followed by dorsal hair removal. Hair regeneration was observed for 12 consecutive days after hair removal. After 12 days, all mice in the two groups were sacrificed, their depilated and non-depilated dorsal skin tissues were resected, and total RNA was extracted from the tissues. Real-time quantitative PCR was performed to determine the mRNA expression of hair keratin genes, vitamin D receptor/β-catenin pathway-related genes, and genes associated with maintenance of hair follicle stem cell proliferation and quiescence. Paraffin-embedded sections of depilated and non-depilated mouse skin tissues were prepared, and immunofluorescence staining was conducted to determine the number of stem cells in the hair follicle bulge. Two-independent-sample t test was used for comparisons between two groups. Results:From days 0 to 12 after depilation, hair regeneration was delayed in the depilated skin area in the knockout group compared with the control group. Real-time quantitative PCR showed significantly decreased mRNA relative expression levels of hair keratin genes Ha1 and Krt2-16, vitamin D receptor/β-catenin pathway-related genes S100a3, Dlx3 and Tubb3, and genes associated with maintenance of hair follicle stem cell proliferation and quiescence including Lhx2, Sox9 and Nfatc1 in the depilated skin tissues in the knockout group (22.09 ± 12.32, 2.07 ± 0.20, 0.02 ± 0.01, 12.36 ± 2.12, 1.75 ± 0.46, 0.39 ± 0.02, 4.42 ± 0.76, 0.44 ± 0.07, respectively) compared with the control group (70.53 ± 9.46, 7.76 ± 0.49, 0.05 ± 0.01, 26.16 ± 2.96, 2.60 ± 0.14, 0.71 ± 0.09, 11.93 ± 0.42, 0.75 ± 0.04, respectively; t = 5.40, 18.64, 3.89, 6.57, 3.04, 6.10, 15.03, 6.18, respectively, all P < 0.05) . Immunofluorescence staining showed that the number of CD34 +K15 + hair follicle stem cells in the hair follicle bulge in both depilated and non-depilated skin tissues was significantly lower in the knockout group than in the control group. Conclusion:Med1 gene knockout may down-regulate the expression of downstream genes of the vitamin D receptor/β-catenin pathway and genes associated with maintenance of hair follicle stem cell proliferation and quiescence (Sox9, Nfatc1 and Lhx2) , and reduce the number of hair follicle stem cells, leading to hair follicle differentiation disorder and hair regeneration delay.

We presented an adolescent with recurrent intracranial hemorrhage and skin lesion. The diagnosis was unclear and the treatment was difficult. Through a multidisciplinary effort type Ⅰ interferon disease was suspected and later, an interferon-stimulated gene was further detected. Considering the high morbidity and fatality rate of recurrent intracranial hemorrhage, tofacitinib and hydroxychloroquine were administered. After treatment, the livedo reticularis was significantly regressed. Unfortunately, the intracranial hemorrhage recurred due to a pre-existing cerebral aneurysm, leading to death of the patient. The diagnosis and treatment of this case highlight the importance of multidisciplinary collaboration in the diagnosis and treatment of difficult and rare diseases.

Objective    To investigate the safety and effectiveness of the multi-artery graf tstrategy for coronary bypass (MICS-CABG) with small incision in the left chest, and to provide experience for the promotion of this technique. Methods    The clinical data of 64 patients with MICS-CABG in Department of Cardiac Surgery of Peking University Third Hospital from December 2015 to November 2019 were retrospectively analyzed. There were 54 males and 10 females, aged 36-77 (61.1±8.7) years. The left lateral thoracic incision (5-8 cm) was made through the 5th intercostal incision, and the operation was performed under off-pump CABG. With the help of the chest wall suspension device and the heart fixator, the proximal anastomosis of the ascending aorta, anastomosis of the target vessels of the left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) systems were completed. The number of grafts was 2-4 (2.3±0.5) including 2 grafts in 45 patients, 3 grafts in 17 patients and 4 grafts in 2 patients. Three patients were treated with percutaneous intervention (PCI) hybridization and 62 patients were treated with total artery bypass graft. Coronary angiography was performed within 7 days after the operation to evaluate the graft patency rate. The incidence of major adverse cardiac and cerebrovascular events (MACCE) was recorded in the follow-up. The MACCE rate was calculated by Kaplan-Meier method. Results    None of the patients was transferred to thoracotomy and no intra-aortic balloon counterpulsation (IABP) or extracorporeal membrane oxygenation (ECMO) was used during the operation.  Incision infection was in 1 patient and reoperation in 2 patients (all were postoperative hemorrhage). Within 30 days after surgery, MACCE occurred in 1 patient, including 1 patient of non-fatal myocardial infarction. The overall patency rate of angiography bypass was 96.2%, and the patency rate of anterior descending branch bypass was 98.2%. Follow-up was performed from 12 to 60 months (median follow-up time was 28 months). The loss rate was 7.8% (5/64). The incidence of MACCE was 84.9% (95%CI 79.5%-90.3%). Conclusion    The MICS-CABG can achieve completed re-vascularization and totally artery-CABG and the short-term and medium-term clinical results of the operation are good.