Xiang thinking is a cognitive approach that reflects the relationships between phenomena and their underlying principles by analyzing their external manifestations through methods such as analogy， reasoning， deduction， and symbolism. This article applied xiang thinking to analyze the etiology and pathogenesis of "wind， fire， phlegm， and blood stasis" in stroke， thereby exploring its impact on the principles of syndrome differentiation and treatment of this condition. Meanwhile， the article traced the construction process of xiang thinking， and interpreted the concept of "toxin pathogen" in traditional Chinese medicine from four perspectives， state， attribute， origin， and law. Furthermore， the relationship between the process of constructing xiang thinking and the origin of etiology， identification methods， pathogenesis evolution， and treatment strategies for stroke with syndrome of combined blood stasis and toxin was explored， so as to provide insights into research on the etiology and pathogenesis of stroke， as well as clinical diagnosis and treatment approaches.

Xiang thinking is the key way of thinking to construct the life model of human body in traditional Chinese medicine （TCM）， and the theory of ascending and descending of qi movement is an important manifestation of xiang thinking in the theory of TCM. Based on the theory of qi movement， this paper interpreted the mechanism of ischemic stroke through the perspective of xiang thinking "earth weakness - wood constraint - fire hyperactivity"， as "earth weakness in the central and dampness accumulated to phlegm" "wood constraint and stirring wind led to blood stasis" and "fire hyperactivity and fire toxin showed flaming upward" due to disorder of qi movement. Combined with the "xiang of medicinal properties and therapy methods" to discuss the treatment and prescriptions of ischaemic stroke， applying wind medicinals to elevate ji-earth （己土） and yi-wood （乙木）， so that phlegm and stasis can be eliminated， and cold medicinals to descend jia-wood （甲木） and wu-earth （戊土） so that fire toxin can be cleared， with a view to restore ascending and descending of qi movement for ischaemic stroke.

Objective To evaluate the feasibility,reliability and validity of the symptom identification scale for kidney yang deficiency syndrome.Methods The symptom identification scale for kidney yang deficiency syndrome developed in previous research was administered to 200 vascular cognitive impairment patients from September 2020 to September 2022 to assess feasibility through recall rate,completion rate,and completion time;reliability was measured using retest reliability,split-half reliability,homogeneity reliability,and inter-rater reliability;and validity was evaluated based on discriminant and structural validity.Results A total of 200 scales were sent out,and all of them cooperated and were completed and retrieved within 20 min.The results of reliability analysis showed that the retest reliability of the scale was 0.828 for the dimension of yang deficiency and 0.718 for the dimension of kidney qi deficiency;the Spearman-Brown coefficient of split-half reliability was 0.784;the Cronbach coefficient of the dimension of yang deficiency was 0.799,and the Cronbach coefficient of the dimension of kidney qi deficiency in the homogeneity reliability was 0.670.The results of the analysis showed that the differences between the kidney yang deficiency syndrome group and the non-kidney yang deficiency syndrome group in the yang deficiency dimension,kidney qi deficiency dimension scores and total scale scores in the discriminant validity were statistically significant(P<0.001);the KMO value in the structural validity was 0.842,and a total of two factors with eigenvalues greater than 1 were extracted,with a cumulative variance contribution rate of 58.227%.Conclusion The symptom identification scale for kidney yang deficiency syndrome demonstrates adequate reliability and validity,potentially enhancing the prediction of kidney yang deficiency in vascular cognitive impairment.However,the validity of the scale is somewhat limited and requires further refinement for clinical application.

ObjectiveTo discuss the thought of treatment of orifices in the Chinese herbal classics in the past dynasties based on the correspondence between drugs and symptoms to guide the clinical treatment based on syndrome differentiation. MethodAll the literature data of Chinese herbal classics were retrieved from the database of the Chinese Medical Dictionary， involving 76 works of Chinese herbal classics and covering representative works from the Han dynasty to the Ming and Qing dynasties. The information on Chines herbal drugs for the treatment of orifices was collected and sorted out. According to Chinese Materia Medica （11^th Edition） and Pharmacopoeia of the People's Republic of China （2020 Edition）， the nature， flavor， and meridian tropism of the selected Chinese herbal drugs were statistically analyzed. The pathogenesis elements in the treatment of orifices were classified and counted， and the contents of syndrome differentiation and treatment in various Chinese herbal classics were extracted. ResultIn 76 Chinese herbal classics in the past dynasties， 93 Chinese herbal drugs for the treatment of orifices were selected. The nature of drugs was mainly warm， followed by cold and mild. The flavor was mainly pungent， followed by bitter and sweet. In terms of meridian tropism， drugs mainly acted on the lung meridian， followed by stomach， heart， liver， spleen， and kidney meridians. The pathogenesis elements of orifices could be divided into six categories， i.e.， wind invasion， turbid obstruction and Qi stagnation， water and dampness stagnation， blood stasis and collaterals blockage， heat and toxin damage， deficiency of vital Qi and cold coagulation. ConclusionOrifices are mainly treated with drugs effective in dispelling wind and pathogenic factors， resolving turbidity and removing stagnation， inducing diuresis and eliminating dampness， promoting blood circulation and dredging collaterals， clearing heat and purging fire， tonifying deficiency and dispelling cold， which are used in combination. Eliminating pathogenic factors and dredging， tonifying deficiency and purging excess are the main characteristics of treatment of orifices based on syndrome differentiation， which is in line with the physiological dysfunction state of orifices in losing the function， evil Qi blockage and healthy Qi deficiency.

As the guiding theory for the diagnosis and treatment of encephalopathy in traditional Chinese medicine （TCM）， The marrow sea theory has important theoretical connotation and clinical value. This paper summarized the clinical research literature on the differentiation and treatment of common encephalopathy based on the marrow sea theory published in recent years， analyzed the treatment method and effects from eight aspects in terms of stroke， dizziness， insomnia， headache， constraint syndrome， dementia， tremor syndrome， and atrophy syndrome， and discussed the possible mechanism based on the relevant basic research. It is believed that marrow sea depletion is the common pathogenesis of encephalopathy in TCM. Guided by the method of supplementing essence and boosting marrow， the corresponding formulas and medicinals are recommended in accordance with differentiated syndromes， which can effectively improve the symptoms of the disease， delay the progression， increase the daily life ability of the patients， and improve the quality of life. Based on the marrow sea theory， the method of supplementing essence and boosting marrow， rectifying healthy qi and dispelling pathogen can be used to highlight the advantages of TCM and provide ideas for the diagnosis and treatment of encephalopathy in TCM.

Objective:To investigate the expression profile of IL-36 family members in patients with coronary atherosclerotic heart disease (CAHD) and to assess the regulatory effects of exogenous IL-36 on CD8 + T cell function in CAHD patients. Methods:Twenty controls and 82 CAHD patients including 31 with stable angina pectoris (SAP), 27 with unstable angina pectoris (UAP) and 24 with acute myocardial infarction (AMI) were enrolled in this study. Anti-coagulant peripheral blood samples were collected. Plasma and peripheral blood mononuclear cells were isolated. The levels of IL-36α, IL-36β, IL-36γ and IL-36 receptor antagonist (IL-36RA) in plasma were measured by ELISA. CD8 + T cells were enriched. The expression of IL-36 receptor subunits at mRNA level was semi-quantified by real time PCR. Flow cytometry was used to detect the expression of programmed death-1 (PD-1), cytotoxic T lymphocytes associated protein-4(CTLA-4) and lymphocyte-activation gene-3 (LAG-3) in CD8 + T cells. Levels of periforin, granzyme B, granulysin, IFN-γ and TNF-α in the culture supernatants of CD8 + T cells were measured by ELISA. Purified CD8 + T cells from controls and AMI patients were stimulated with recombinant human IL-36RA. Changes in the expression of immune checkpoint molecules and the secretion of cytotoxic molecules and cytokines after IL-36RA stimulation were analyzed. One-way analysis of variance or paired t-test was used for statistical analysis. Results:There were no significant differences in plasma IL-36α, IL-36β or IL-36γ level between the control, SAP, UAP and AMI groups ( P>0.05). Plasma IL-36RA level was significantly down-regulated in the AMI group as compared with that in the control, SAP and UAP groups[(1 159.57±297.83) pg/ml vs (1 773.47±754.29) pg/ml, (1 600.12±740.48) pg/ml and (1 578.72±720.42) pg/ml; P<0.05]. The expression of IL-1 receptor 6 (IL-1R6) and IL-1 receptor accessory protein (IL-1RAcP) at mRNA level, the expression of PD-1 and CTLA-4, and the secretion of IFN-γ and TNF-α by CD8 + T cells showed no significant differences between the four groups ( P>0.05). Periforin, granzyme B and granulysin levels secreted by CD8 + T cells of the AMI group were significantly higherthan those of the control, SAP and UAP groups ( P<0.05). In the control group, recombinant human IL-36RA stimulation did not affect the expression of immune checkpoint molecule or the secretion of cytotoxic molecules and cytokines by CD8 + T cells ( P>0.05). In the AMI group, the percentage of PD-1 + CD8 + T cells increased after recombinant human IL-36RA stimulation ( P=0.033), but no significant change in the percentage of CTLA-4 + CD8 + T cells was observed ( P=0.288). Moreover, recombinant human IL-36RA stimulation suppressed the CD8 + T cells of AMI patients to secrete periforin, granzyme B and granulysin ( P<0.05), but not affect the secretion of IFN-γ and TNF-α ( P>0.05). Conclusions:The reduced IL-36RA level in AMI patients might induce the enhancement of CD8 + T cell activity by promoting CD8 + T cells to secrete cytotoxic molecules, which was involved in the immunopathogenesis of AMI.

Objective:To explore the prescription and medication law of Traditional Chinese Medicine (TCM) compounds in the treatment of vascular dementia (VD) based on patent database.Methods:TCM compounds with patents about VD were retrieved from Chinese patent announcement website of the State Intellectual Property Office and CNKI. The retrieval time was from the establishment to the databases to 31 st, March 2022. The frequency, clusteringand association analysis were carried out with the help of TCM inheritance auxiliary platform (V2.5). The medication law was analyzed. Results:154 TCM compound patents for the treatment of vascular dementia were screened, involving 227 kinds of Chinese materia medica. Among them, Acori Tatarinowii Rhizoma (44 times, 28.57%) was used more frequently, and the common medicinal pair was Salviea Miltiorrhizae Radix et Rhizoma- Acori Tatarinowii Rhizoma (17 times, 11.03%). The medicinal property was mainly warm, the taste was mainly sweet, and the meridian was mainly liver meridian. Those with high confidence based on association rules were " Corni Fructus -Acori Tatarinowii Rhizoma" (0.90), " Corni Fructus -Rehmannize Radix et Praeparata" (0.90). Based on the complex network, it was concluded that the core drugs were 14 groups such as " Rehmannize Radix et Praeparata- Cistanches Herba- Corni Fructus". The new prescriptions extracted by entropy cluster analysis included 7 groups such as " Rehmannize Radix et Praeparata, Cistanches Herba, Corni Fructus and Asparagi Radix". Conclusion:The treatment of VD by TCM compounds with national patents is mainly based on tonifying deficiency, promoting blood circulation and removing blood stasis, eliminating phlegm and dampness, expelling wind and dredging collaterals, opening orifices and resuscitation, which can provide reference for clinical practice and new drug research and development.

Objective : To explore the effect of hydroxy⁃carboxylic acid receptor 2 (HCAR2) on erythroid differen⁃ tiation of human chronic myeloid leukemia K562 cells under hypoxia . Methods : The cells were cultured in medium containing hemin to compare the ability of K562 cells to differentiate into erythroid cells under normoxia/hypoxia conditions . Then the expression of HCAR2 was interfered with genetic methods to knockdown or overexpress it in K562 cells , respectively . Benzidine staining , RT⁃qPCR , Western blot and flow cytometry were used to detect the role of HCAR2 in the erythroid differentiation of K562 promoted by hypoxia . Results : On day 1 , 2 , 3 after differentiation , the expression level of HCAR2 and the erythroid differentiation， the expression level of HCAR2 and the erythroid differentiation ability of K562 cells increased gradually with time , and hypoxia enhanced the above phenotypes compared with normoxia . In HCAR2⁃silenced K562 cells , erythroid cells was reduced and the expression of erythroid differentiation markers CD235a and γ⁃globin decreased . Simultaneously , the proportion of double⁃positive cells expressing erythroid cell surface molecules CD71 and CD235a was lower than that of the control group . On the contrary , the overexpression of HCAR2 in K562 cells increased erythroid cells generation as well as elevated the expression levels of CD235a and γ⁃globin . In addition , the proportion of CD71 /CD235a double⁃positive cells also increased in HCAR2⁃overexpressed K562 cells . Conclusion HCAR2 mediates hypoxia in promoting the erythroid differentiation of K562 cells .

Objective:To evaluate clinical efficacy and safety of topical compound oleum lithospermi in the treatment of mild to moderate diaper dermatitis.Methods:A multicenter, randomized, positive-drug parallel-controlled clinical trial was conducted in 19 hospitals from July 2019 to August 2020. Children aged 0 - 12 months with mild to moderate diaper dermatitis were enrolled and randomly divided into 2 groups using a random number table: test group topically treated with compound oleum lithospermi, and control group topically treated with zinc oxide cream. The treatment was carried out 6 - 8 times a day for 7 days. Visits were scheduled on days 0 and 7, and total response rate and clinical healing time were evaluated. Changes in the dermatitis family impact (DFI) score were compared between the test group and control group, and adverse events were recorded. Statistical analysis was carried out by using independent-sample t test for normally distributed continuous data, Wilcoxon rank sum test for non-normally distributed continuous data, and chi-square test or Fisher′s exact test for unordered categorical data; survival curves were drawn, and log-rank test was used for comparisons between two groups. Results:A total of 343 children with diaper dermatitis were enrolled in this study. Among them, 31 children violated the protocol, so 312 were included in the per protocol set, including 157 in the test group and 155 in the control group, and all completed the visits on days 0 and 7. The total response rate was significantly higher in the test group (87.26%, 137/157) than in the control group (78.71%, 122/155; χ2 = 4.04, P = 0.044) . The clinical healing time was significantly shorter in the test group (5.33 days) than in the control group (6.13 days; χ2 = 4.67, P = 0.025) . After 7-day treatment, the DFI score significantly decreased in both the 2 groups compared with that before the treatment, but there was no significant difference in the DFI score between the 2 groups (test group: 4.02 ± 6.96, control group: 3.58 ± 5.90, Z = -0.39, P = 0.686) . The incidence of adverse events was 2.92% (5/171) and 5.45% (9/165) in the test group and control group respectively, and there was no significant difference between the 2 groups ( χ2 = 0.03, P = 0.865) . Conclusion:Compound oleum lithospermi can markedly reduce the clinical severity of diaper dermatitis, improve the total response rate, shorten the clinical treatment period, and improve the quality of life of children′s families with a favorable safety profile.

Objective: To provide guidelines for the prevention of post-stroke dementia, we investigated whether stroke patients were aware of post-stroke dementia and their level of dementia-related knowledge. Methods: Five dementia-related questions were designed. A field survey was conducted in a question-and-answer method using the designed questions. The surveys assessed 3000 stroke patients (2 weeks-6 months after stroke attacks) from 14 hospitals/clinical centers in 7 provinces and cities across China. Results: Among 3000 stroke patients, 80.5％had heard of dementia, 39.1％knew that stroke can lead to dementia, 55.7％ believed dementia can be prevented, 50.8％ thought dementia can be cured, and only 8.8％had ever seen a doctor because of memory deterioration. Then, patients were classified into three groups, including a no cognitive impairment (NCI) group, a mild cognitive impairment (MCI) group, and a mild dementia (MD) group. Among the MCI and MD groups, only 8.7％ (75/861) and 9.9％ (64/649) of patients, respectively, had ever seen a doctor because of memory deterioration. According to our results, patients with a higher level of cognitive impairment had a lower awareness of dementia (P<.001). Conclusion: The awareness of dementia in stroke patients in China is low, and the consultation rate is even lower. Moreover, patients with a higher level of cognitive impairment have a lower awareness of dementia. To improve public awareness and improve prevention, more emphasis should be put on ed-ucation regarding post-stroke dementia. Routine cognitive function screening should be conducted on stroke patients as an effective way to assess dementia.