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.

Aortic dissection is a life-threatening cardiovascular disease with devastating complications and high mortality. It requires rapid and accurate diagnosis and a focus on prognosis. Many laboratory tests are routinely performed in patients with aortic dissection including D-dimer, brain natriuretic peptide, cardiac troponin I, C-reactive protein, and procalcitonin. D-dimer shows vital performance in the diagnosis of aortic dissection, and brain natriuretic peptide, cardiac troponin I, C-reactive protein, and procalcitonin exhibits important value in risk stratification and prognostic effect in aortic dissection patients. Our review summarized the clinical utility of these laboratory tests in patients with aortic dissection, aiming to provide advanced and comprehensive evidence for clinicians to better understand these laboratory tests and help their clinical practice.

Objectives:To investigate the distribution and change of the burden of cardiovascular diseases attributable to tobacco consumption in China and the world from 1990 to 2021.Methods:Based on Global Burden of Disease(GBD)2021 database,age standardized mortality and age standardized disability-adjusted life year(DALY)rates and estimated annual percentage change(EAPC)from cardiovascular disease(including ischemic heart disease,stroke,atrial fibrillation and flutter,aortic aneurysm,peripheral artery disease)attributable to tobacco consumption were analyzed.The association of the human development index(HDI)and social demographic index(SDI)with age-standardized mortality was also analyzed.Results:Compared to 1990,the global burden of cardiovascular diseases attributable to smoking declined in 2021,age-standardized mortality decreased from 57.2/100 000 to 26.3/100 000(EAPC=-1.81%,95% CI:-2.00% to-1.63% ).The global burden of cardiovascular diseases attributable to second-hand smoke also decreased,age-standardized mortality decreased from 11.4/100 000 to 8.3/100 000(EAPC=-1.72%,95% CI:-1.91% to-1.53% ).In China,the burden of cardiovascular diseases attributable to smoking also decreased,age-standardized mortality decreased from 52.2/100 000 to 39.6/100 000(EAPC=-1.23%,95% CI:-1.44%-1.02% );the burden of cardiovascular diseases attributable to second-hand smoke decreased,age-standardized mortality decreased from 15.3/100 000 to 14.7/100 000(EAPC=-1.26%,95% CI:-1.63% to-0.90% ).Notably,the decrease in cardiovascular diseases burden attributable to second-hand smoke among Chinese women was more significant than the global level,the age-standardized mortality rate of Chinese women decreased from 17.9/100 000 to 14.5/100 000(EAPC=-2.24%,95% CI=-2.78%～-1.86% ).Among the five types of cardiovascular diseases attributable to tobacco consumption globally and in China,the age-standardized mortality and age-standardized DALY rates of aortic aneurysm,ischemic heart disease and peripheral artery disease were higher.Globally,ischaemic heart disease is the leading cause of death,accounting for 60.2% in 1990 and 61.7% in 2021,while stroke is the leading cause of death in China,accounting for 68.1% and 51.4% in 1990 and 2021,respectively.In addition,HDI and SDI are the two main factors affecting the disease burden.In regions and countries with SDI>7.2,age standardized mortality is below our forecast line.In the later part of the forecast,China's age standardized mortality showed a downward trend,possibly due to changes in tobacco control measures.Conclusions:Over the past 30 years,the burden of cardiovascular diseases attributed to tobacco consumption has decreased globally and in China.The decline in disease burden has been most pronounced among women.However,in countries and regions with an SDI below 7.2,the burden of disease remains significant high.Therefore,it is necessary to take tobacco control measures in key regions(China,East Asia,Central Europe,Central Asia and Southeast Asia)to actively reduce smoking rates and exposure to secondhand smoke in public places,so as to reduce the burden of cardiovascular diseases.

Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P＜0.05,P＜0.001),but did not up-regulate the expression of Beclin1(P＞0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P＜0.05,P＜0.05,P＜0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulated the expression of Beclin1(P＞0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulate the expression of Beclin1(P＞0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.

Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P＜0.05,P＜0.001),but did not up-regulate the expression of Beclin1(P＞0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P＜0.05,P＜0.05,P＜0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulated the expression of Beclin1(P＞0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P＜0.01,P＜0.01,P＜0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P＜0.05,P＜0.01),but did not upregulate the expression of Beclin1(P＞0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.

Objectives:To investigate the distribution and change of the burden of cardiovascular diseases attributable to tobacco consumption in China and the world from 1990 to 2021.Methods:Based on Global Burden of Disease(GBD)2021 database,age standardized mortality and age standardized disability-adjusted life year(DALY)rates and estimated annual percentage change(EAPC)from cardiovascular disease(including ischemic heart disease,stroke,atrial fibrillation and flutter,aortic aneurysm,peripheral artery disease)attributable to tobacco consumption were analyzed.The association of the human development index(HDI)and social demographic index(SDI)with age-standardized mortality was also analyzed.Results:Compared to 1990,the global burden of cardiovascular diseases attributable to smoking declined in 2021,age-standardized mortality decreased from 57.2/100 000 to 26.3/100 000(EAPC=-1.81%,95% CI:-2.00% to-1.63% ).The global burden of cardiovascular diseases attributable to second-hand smoke also decreased,age-standardized mortality decreased from 11.4/100 000 to 8.3/100 000(EAPC=-1.72%,95% CI:-1.91% to-1.53% ).In China,the burden of cardiovascular diseases attributable to smoking also decreased,age-standardized mortality decreased from 52.2/100 000 to 39.6/100 000(EAPC=-1.23%,95% CI:-1.44%-1.02% );the burden of cardiovascular diseases attributable to second-hand smoke decreased,age-standardized mortality decreased from 15.3/100 000 to 14.7/100 000(EAPC=-1.26%,95% CI:-1.63% to-0.90% ).Notably,the decrease in cardiovascular diseases burden attributable to second-hand smoke among Chinese women was more significant than the global level,the age-standardized mortality rate of Chinese women decreased from 17.9/100 000 to 14.5/100 000(EAPC=-2.24%,95% CI=-2.78%～-1.86% ).Among the five types of cardiovascular diseases attributable to tobacco consumption globally and in China,the age-standardized mortality and age-standardized DALY rates of aortic aneurysm,ischemic heart disease and peripheral artery disease were higher.Globally,ischaemic heart disease is the leading cause of death,accounting for 60.2% in 1990 and 61.7% in 2021,while stroke is the leading cause of death in China,accounting for 68.1% and 51.4% in 1990 and 2021,respectively.In addition,HDI and SDI are the two main factors affecting the disease burden.In regions and countries with SDI>7.2,age standardized mortality is below our forecast line.In the later part of the forecast,China's age standardized mortality showed a downward trend,possibly due to changes in tobacco control measures.Conclusions:Over the past 30 years,the burden of cardiovascular diseases attributed to tobacco consumption has decreased globally and in China.The decline in disease burden has been most pronounced among women.However,in countries and regions with an SDI below 7.2,the burden of disease remains significant high.Therefore,it is necessary to take tobacco control measures in key regions(China,East Asia,Central Europe,Central Asia and Southeast Asia)to actively reduce smoking rates and exposure to secondhand smoke in public places,so as to reduce the burden of cardiovascular diseases.

The Republic of China period （1912—1949） was an important stage of transition from traditional herbalism to clinical Chinese materia medica. The clinical application of Chinese materia medica became the focus of academic attention. During the Republic of China period， the research objectives， methods， and content of clinical Chinese materia medica were clarified， and the basic framework of Chinese materia medica was established through efficacy classification and item description. Based on the historical background at that time， striving for survival in adversity were the internal factors driving the construction of clinical Chinese materia medica， and the rise of academic education and the popularity of traditional Chinese medicine journals provided favorable conditions for the development of clinical Chinese materia medica. The clinical Chinese materia medica during the Republic of China period gradually formed a theoretical structure and core content that was distinctly different from that of traditional herbal medicine， which was integrated with the scientific research of Chinese materia medica and promoted the continuous development of Chinese materia medica together with other subdisciplines， presenting distinctive characteristics of the times and important academic significance.

ObjectiveTo comprehensively evaluate the clinical value of Feilike mixture and provide a basis for the allocation of medical resources， rational drug use， and hospital procurement and supply of Chinese patent medicines. MethodWith the data from available studies and provided by drug manufacturers， the methods of evidence-based medicine， pharmacoeconomics， and health technology assessment were employed to construct a multi-criteria decision-making analysis framework from the "6+1" dimensions of safety， effectiveness， economy， innovation， suitability， accessibility， and characteristics of traditional Chinese medicine （TCM）. The clinical evidence and value evaluation software of Chinese patent medicine， CSCv2.0， was used to comprehensively evaluate the clinical value of Feilike mixture. ResultBased on the existing clinical evidence， the following results were obtained. ① Safety： Multi-sources of evidence showed that Feilike mixture had little known risk and sufficient evidence， with the safety rated as grade A， which indicated good safety. ② Effectiveness： The systematic review and Meta-analysis showed that Feilike mixture combined with conventional Western medicine in the treatment of bronchitis shortened the time to disappearance of cough compared with conventional Western medicine alone， with the evidence rated as grade B by the Grading of Recommendations Assessment， Development， and Evaluations （GRADE） system， which indicated high effectiveness. ③ Economy： From the perspective of health system， Feilike mixture combined with conventional Western medicine was more economical than conventional Western medicine alone， and the quality evaluation of pharmacoeconomics rated the economy as grade B. ④ Innovation： Feilike mixture combined with conventional Western medicine improved the clinical treatment effect and had innovation advantages compared with similar drugs. From the aspects of cultivation， identification of medicinal materials， and production， the sufficient supply and safety of medicinal materials can be ensured for Feilike mixture. This medicine was rated as grade B in terms of the medicinal material quality， preparation technology， and patents， which indicated good innovation. ⑤ Suitability： According to the results of the questionnaire survey， the usage of Feilike mixture was easy to be mastered and accepted by doctors and nurses， without special administration time， complex personalized treatment， and special technical and management requirements. It is convenient for patients to use， with convenient supply and storage， and weak influences of policy， publicity， and drug information. Therefore， the suitability of Feilike mixture was rated as grade B. ⑥ Accessibility： Among the similar Chinese patent medicines， Feilike mixture had a moderate price， high production capacity， wide sales coverage， wide coverage of hospitals， sustainable supply of medicinal materials， and low costs of treatment for acute bronchitis， with the accessibility rated as grade A. ⑦ TCM characteristics： Feilike mixture is composed of Scutellariae Radix， Peucedani Radix， Stemonae Radix， Gentianae Rhodanthae Herba， Scleromitrion diffusum， Firmiana platanifolia Radix， and Aster ageratoides， with reasonable compatibility. This formula is derived from the medical experience of Miao ethnic group， with rich experience in human use and the TCM characteristics rated as grade B. According to the evaluation results in the "6+1" dimensions， Feilike mixture was evaluated as class B， with a high clinical value. ConclusionAccording to the existing clinical evidence， compared with conventional Western medicine alone， Feilike mixture combined with conventional Western medicine demonstrates a high clinical value and prominent TCM characteristics in the treatment of acute bronchitis with phlegm-heat invading lung. It is suggested that it should be translated into the basic clinical drug management policy results according to the conditions.

The treatment of acute Stanford type A aortic dissection has always been extremely challenging. Organ malperfusion syndrome is a common severe complication of acute aortic dissection, which can cause organ ischemia and internal environment disorder. Malperfusion increases early mortality, and impacts the long-term prognosis. In recent years, many scholars have done some studies on aortic dissection complicated with malperfusion. They explored the pathogenesis, proposed new classification, and innovated new treatment strategies. However, at present, the treatment strategies of acute Stanford type A aortic dissection complicated with organ malperfusion are different at different centers and consensus on its treatment is still lacking. Therefore, this review summarized the pathogenesis, classification, treatment strategy, and prognosis of acute Stanford type A aortic dissection complicated with malperfusion.

BACKGROUND:Oleic acid can regulate inflammation and immune responses,and has the potential to repair skin wounds.Oleic acid has a short retention time at the lesion.It is prone to self oxidation and deterioration in the air,and suitable drug carriers are needed to fully exert the therapeutic effect of oleic acid. OBJECTIVE:To investigate the efficacy of oleic acid-liposome gel in the treatment of chronic burn wounds. METHODS:Oleic acid liposome solution was prepared by thin film dispersion method,and then dissolved in Poloxamer gel matrix to prepare oleic acid-liposome gel.(1)In vitro experiment:Oleic acid-liposome gel solution was prepared by adding different volumes of oleic acid-liposome gel into cell medium(volume ratio:1:3,1:9,1:27,respectively).Alma-blue reagent was used to detect the effects of different concentrations of oleic acid-liposome gel on the proliferation of human keratinocytes and human fibroblasts.Crystal violet staining was used to observe cell morphology.(2)In vivo experiment:The animal model of chronic burn wounds was established by using full-thickness burn of SD rat back skin combined with local subcutaneous injection of epirubicin.The 30 successfully modeled rats were randomly divided into five groups with six rats in each group.The wounds of oleic acid liposome gel group,oleic acid group,liposome gel group,positive control group and negative control group were applied with gauze of oleic acid liposome gel,oleic acid,liposome gel,recombinant human epidermal growth factor gel and normal saline.The dressing was changed once every other day.A total of 16 doses were administered.The wound healing was observed. RESULTS AND CONCLUSION:(1)In vitro experiments:Alma-blue reagent detection and crystal violet staining showed that oleic acid liposome gel solution with volume ratio of 1:9 could promote the proliferation of human keratinocytes and human fibroblasts.(2)In vivo experiment:The wound healing time of the oleic acid liposome gel group was shorter than that of the other four groups(P＜0.01),and the wound healing rate at 4,8,12,16,and 20 days was higher than that of the other four groups(P＜0.01).After administration,hematoxylin-eosin staining showed epithelialization and healing of wounds in all five groups,and the epidermal thickness of oleic acid liposome gel group was the closest to normal skin and better than the other four groups.Immunohistochemical staining showed that the expressions of cytokeratin 10,tumor protein 63,α-smooth muscle actin,collagen I,tumor necrosis factor α,interleukin 6,malonaldehyde,and superoxide dismutase in oleic acid liposome gel group were closest to those in normal skin,and superior to those in other four groups.On days 12 and 32 of administration,the expressions of tumor necrosis factor α,interleukin 6,malondialdehyde,and superoxide dismutase in wound homogenate supernatant in oleic acid liposome gel group were closest to those in normal skin,and superior to those in other four groups.(3)The results showed that oleic acid liposome gel could promote the proliferation of keratinocytes and fibroblasts,reduce inflammation and oxidative stress injury,and promote the healing of chronic burn wounds.