From the perspective of dynamic and static concept in traditional Chinese medicine， we explored the pathogenesis and treatment of attention deficit hyperactivity disorder （ADHD）. ADHD is categorized into "dynamic type" and "static type" based on symptom presentation. It is believed that the core disease mechanism of static type ADHD refers to insufficiency of essence and blood， as well as the loss of nourishment of brain marrow and heart blood； the dominant mechanism of dynamic type ADHD refers to excessive use of the mind and improper diet lead to the excessive movement of dragon-thunder fire （symbolizing hyperactivity）. The treatment should first differentiate between static type and dynamic type. The treatment for static type focuses on the spleen and kidney， and involves replenishing the acquired constitution to nourish the congenital， supporting the heart and spirit， and enriching the brain and marrow， so as to ensure sufficient qi and blood， abundant essence and strong spirit， thereby improving symptoms of attention deficits. The dynamic type should be treated by static method， and involves using calming medicinals to supplement， transform， and subdue to reach the aims of enriching yin and subduing yang， warming and supplementing the spleen and kidney， which helps restore the dragon-thunder fire to its balance. Based on the physiological characteristics of children， a dynamic-static differentiation and treatment system is established to provide a reference for the clinical treatment of ADHD.

ObjectiveTo develop the Evidence Grading Scale for Ancient classical prescriptions in Traditional Chinese medicine， assess its reliability and validity， and apply it in practice to provide multi-source evidence for clinical practice guidelines development. MethodsLiterature retrieval was conducted to extract and screen existing evaluation dimensions， then the initial items were summarized using thematic analysis. Experts in the clinical medicine， medical history and literature participated in the Delphi questionnaire survey to evaluate and refine the items. An expert consensus meeting was conducted to finalize the included items， refine the method for items evaluation and evidence grading. The evidence quality rating scale for ancient classical traditional Chinese medicine （TCM） prescriptions was then established and tested for reliability and validity. ResultsThrough literature review， extraction， screening and summarization， a total of 3 dimensions and 12 initial items were formed. Questionnaires were sent to 69 experts to evaluate the initial items， with a questionnaire response rate of 100% and an expert authority coefficient of 0.92. All 12 items were retained for they had importance scores above 4. The Evidence Grading Scale on Ancient classical prescriptions in Traditional Chinese medicine includes 3 dimensions with 12 items. The 3 dimensions includes ancient evidence， inheritance status， and modern application. Each dimension contains 4 items， and each item has a full score of 5 points. The evidence was rated as high-level， moderate-level， and low-level according to the final scores. The content validity index （CVI） of the 12 items was ＞0.9， the average CVI of the scale was 0.98， and the intraclass correlation coefficient （ICC） was 0.90. ConclusionThe Evidence Grading Scale on Ancient classical prescriptions in Traditional Chinese medicine has good reliability and validity， which is practical for use in the development of TCM clinical guidelines and can better support clinical decision-making.

ObjectiveTo construct a rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）， and evaluate the macroscopic manifestations and microscopic indicators of the model. MethodsTwenty-two SD rats were divided into normal group （n=3）， common psoriasis group （n=5）， spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）， and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group （n=7）. The spleen deficiency and dampness obstruction syndrome （external dampness type） rat model was established through 32-week exposure to an artificially simulated high-humidity environment， while the common psoriasis model was developed via 7-day topical application of imiquimod cream， and these two approaches were combined to construct a composite model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type）. Rats in the normal group were housed under normal humidity conditions. The general state， tongue manifestation of rats were observed to evaluate the macroscopic syndrome manifestations； the microscopic syndrome manifestations of rats were evaluated through adipose tissue and liver tissue changes； the severity of psoriasis in rats was evaluated through skin pathological changes， psoriasis area and severity index （PASI）， proliferating cell nuclear antigen （PCNA） expression and spleen tissue changes； changes in rat CD4⁺ interferon-γ⁺ cells （CD4⁺IFN-γ⁺ cells）， CD4⁺ tumour necrosis factor-α+ cells （CD4⁺ TNF-α⁺ cells）， and forkhead framing protein P3⁺ regulatory T cells （CD3⁺CD4⁺FoxP3⁺ Treg cells） were detected by flow cytometry. ResultsMacroscopically， both the spleen deficiency and dampness obstruction syndrome （external dampness type） group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited manifestations of spleen deficiency and dampness obstruction， including lethargy， huddling behavior， dull and disheveled fur， as well as soft or loose stools and perianal soiling in some individuals； both these two groups displayed enlarged tongue， swollen， and moist tongue texture， accompanied by slippery tongue surface. Microscopically， compared to the common psoriasis group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group showed increased epididymal fat index （P＜0.05）； compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group， the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group demonstrated significantly elevated spleen mass （P＜0.05）， while hepatic gross morphology and HE staining revealed no significant histopathological changes across all groups. Dorsal skin lesions were markedly exacerbated in the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group when compared to those in common psoriasis group. Both the common psoriasis group and psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group exhibited significantly higher erythema scores， scaling scores， infiltration scores， PASI total scores， and proportions of CD3⁺CD4⁺FoxP3⁺Treg cells compared to the normal group and spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）， with pronounced PCNA-positive expression observed in the epidermal basal layer and dermis； the psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） group displayed significantly increased proportions of CD4⁺TNF-α⁺cells compared to the spleen deficiency and dampness obstruction syndrome （external dampness type） group （P＜0.05）； whereas no significant differences were detected in CD4⁺IFN-γ⁺cell proportions among groups （P＞0.05）. ConclusionThe rat model of psoriasis with spleen deficiency and dampness obstruction syndrome （external dampness type） can be successfully constructed by artificially simulating a high-humidity environment combined with imiquimod induction.

Objective To investigate the plasma levels of methylated DNA in the pregnant women with preeclampsia and its predictive value for the occurrence of preeclampsia.Methods A total of 82 pregnant women with preeclampsia admitted to the hospital from January to December 2022 were included as the obser-vation group,and another 82 healthy pregnant women were included as the control group.Total DNA was ex-tracted,and the relative expression levels of methylated single-intention homolog 2(SIM2),guanine nucleo-tide-binding protein(GNA12),and connective tissue growth factor(CTGF)genes in plasma were detected by real-time fluorescence quantitative PCR(qRT-PCR)after DNA bisulfite modification.The value of methyla-ted DNA in predicting preeclampsia was evaluated by correlation analysis and receiver operating characteristic(ROC)curve.Results The relative expression levels of methylated SIM2,GNA12 and CTGF in plasma in the observation group were significantly higher than those in the control group(P＜0.05),and the relative expres-sion levels of methylated SIM2,GNA12 and CTGF in severe preeclampsia group was higher(P＜0.05).Corre-lation analysis showed that the relative expression levels of methylated SIM2,GNA12 and CTGF in plasma were significantly positively correlated with the occurrence of preeclampsia in pregnant women(P＜0.05).ROC curve analysis results showed that the relative expression levels of plasma methylation SIM2,GNA12,and CTGF,both individually and in combination,had good predictive efficacy in predicting preeclampsia in pregnant women,and the combined detection of the three had the highest predictive efficacy(area under the curve was 0.888,95％CI:0.827-0.949).Conclusion Compared with healthy pregnant women,the relative expression levels of methylated SIM2,GNA12 and CTGF in plasma are higher in pregnant women with pre-eclampsia,which are positively correlated with the occurrence of preeclampsia and the severity of the disease.The relative expression levels of methylated SIM2,GNA12 and CTGF are expected to be important predicting indicators for preeclampsia.

Objective To investigate the relationship between the expression of keratin 15(KRT15)and keratin 18(KRT18)proteins in colorectal cancer tissue and their clinicopathological features and prognosis.Methods A total of 97 patients with colorectal cancer who underwent surgical treatment in a hospital from June 2018 to June 2019 were selected as the study objects.Immunohistochemistry was used to detect the ex-pression of KRT15 and KRT18 protein in colorectal cancer tissues and adjacent tissues,and the differences of KRT15 and KRT18 protein expression in colorectal cancer patients with different clinicopathological features were compared.The patients with colorectal cancer were followed up for 3 years after discharge,and their o-verall survival(OS)during the follow-up period was analyzed.Kaplan-Meier survival curve and Log-rank test were used to analyze the difference in OS rate among colorectal cancer patients with different KRT15 and KRT18 protein expression.Univariate and multivariate COX proportional regression analysis was performed to analyze the factors affecting the prognosis of patients with colorectal cancer.Results The positive expres-sion rates of KRT15 and KRT18 protein in colorectal cancer tissues were higher than those in adjacent tis-sues,and the difference was statistically significant(P＜0.05).The positive expression rates of KRT15 and KRT18 protein in colorectal cancer tissues of patients with low differentiation,TNM Ⅲ stage,perineural inva-sion and preoperative carcinoembryonic antigen(CEA)level ≥5 ng/mL were higher than those of patients with medium-high differentiation,TNM Ⅰ-Ⅱ stage,without perineural invasion and preoperative CEA level＜5 ng/mL,the difference was statistically significant(P＜0.05).The 3-year OS rates of colorectal cancer patients with positive expression of KRT15 and KRT18 protein were 64.29％and 60.00％respectively,which were lower than those of patients with negative expression of KRT15 and KRT18 protein(83.64％and 85.96％respec-tively),and the difference was statistically significant(x2=6.497,7.987,P＜0.05).Multivariate COX pro-portional regression analysis showed that TNM stage Ⅲ,positive expression of KRT15 protein and positive expression of KRT18 protein were risk factors affecting the survival of patients with colorectal cancer(P＜0.05).Conclusion The expression of KRT15 and KRT18 protein in colorectal cancer tissues can provide ref-erence for prognosis assessment of patients with colorectal cancer.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.

OBJECTIVE To explore the effects of ursolic acid （UA） on the growth， invasion， apoptosis and metastasis of human colorectal cancer cells SW620 and find out the underlying molecular mechanisms. METHODS The effects of different concentrations （0， 5， 10， 15， 20， 25， 30 μmol/L） of UA on the proliferation of SW620 cells for different durations （24， 48， 72 h） were detected by CCK-8 assay； the clone formation was detected by clone formation assay after SW620 cells were treated with different concentrations of UA （0，10，15，20 μmol/L） for 10 days. After SW620 cells were treated with different concentrations of UA （0， 10， 15， 20 μmol/L） for 24 hours， flow cytometry， Transwell invasion assay and Western blot assay were adopted to detect apoptosis and invasion of SW620 cells， and the expressions of B cell lymphoma 2 （Bcl-2）， cleaved-poly （ADP-ribose） polymerase （cleaved-PARP）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， p38 MAPK， E-cadherin， N-cadherin and zinc finger transcription factor Snail. The effects of p38 MAPK inhibitor （SB203580） combined with UA on the protein expressions of p-p38 MAPK， Bcl-2 and N-cadherin were investigated. RESULTS Compared with 0 μmol/L UA， the stone5999@163.com survival rates of SW620 cells treated with 5-30 μmol/L UA for 24， 48 and 72 h were significantly decreased （P＜0.05）. The clone formation rate of cells treated with 15 μmol/L and 20 μmol/L UA was significantly decreased （P＜0.05）. After being treated with 15 μmol/L and 20 μmol/L UA， the cell apoptosis rate， the protein expressions of cleaved-PARP and E-cadherin， and the phosphorylation of p38 MAPK protein were increased； but the number of transmembrane cells， and the protein expressions of Bcl-2， Snail and N-cadherin were decreased； there was statistical significance in difference of most indexes （P＜0.05）. Some indexes changed in a concentration-dependent manner （P＜0.05）. SB203580 could significantly inhibit the upregulation of p38 MAPK by UA and reverse the inhibitory effect of UA on the protein expressions of Bcl-2 and N-cadherin （P＜0.05）. CONCLUSIONS UA can inhibit the growth， invasion and metastasis of SW620 cells， and induce cell apoptosis， the mechanism of which may be attributed to the activation of p38 MAPK signaling pathway.

ObjectiveTo investigate the regulatory effect of Changju Zhidong prescription on gut microbiota structure of children with tic disorder（TD）. MethodTwenty-four children with TD who visited the pediatric outpatient clinic of Dongzhimen Hospital of Bejjing University of Chinese Medicine from November 2020 to January 2022 were selected as the observation group， and eight healthy children were selected as the normal group. The observation group was treated with Changju Zhidong prescription for 12 weeks， and the clinical efficacy was observed by Yale global tic severity scale（YGTSS）， traditional Chinese medicine（TCM） syndrome score， and score of TCM symptom evaluation scale for pediatric gastrointestinal tract. Meanwhile， The fecal samples of the observation and normal groups were collected before and after treatment， and 16S rDNA sequencing was used to explore the effects of Changju Zhidong prescription on the distribution of gut microbiota of the children. ResultCompared with the pre-treatment， the YGTSS， TCM syndrome score， and score of TCM symptom evaluation scale for pediatric gastrointestinal tract of the observation group were significantly reduced after 12 weeks of treatment（P<0.05）， Simpson and Pieloue indices in alpha diversity were significantly reduced（P<0.05）. Before treatment， the relative abundance of Streptococcus parasanguini in the observation group was significantly higher than that of the normal group， while the relative abundances of Citrobacter， Lactobacillus， Lacticaseibacillus， Muribaculaceae unclassified， Odoribacter and 7 other bacterial groups were significantly lower than that in the normal group. Compared with the pre-treatment， the observation group showed a significant decrease in Ruminococcus torques group unclassified and Ruminococcus torques group， and a significant increase in Olsenella， Acetivibrio and 4 other bacterial groups. Functional enrichment analysis showed that the main pathways of Changju Zhidong prescription regulating gut microbiota were bacterial secretion system， insect hormone biosynthesis， limonene and pinene degradation， novobiocin biosynthesis， tropane piperidine and pyridine alkaloid biosynthesis. ConclusionThe pathogenesis of children with TD is accompanied by intestinal flora disorders， and Changju Zhidong prescription can improve core and gastrointestinal symptoms， increase the abundance of beneficial and decrease the abundance of harmful gut microbiota in children with TD， and its mechanism may be through the metabolism of terpenoids and polyketides.

ObjectiveTo elucidate the underlying mechanism of the efficacy of Levo-tetrahydropalmatine （l-THP） in alleviating chronic pain and identify the key metabolites and metabolic pathways for l-THP regulation. MethodA classical chronic constrictive injury （CCI） model was built in rats’ bodies， and the pain intensity was evaluated by detecting the mechanical withdrawal threshold. On the sixth day after surgery， oral administration of l-THP （64 mg·kg^-1） and positive control drug pregabalin （Pre， 30 mg·kg^-1） was performed on rats. After the last administration following consecutive five times of administration， ipsilateral spinal cord tissues were collected for widely-targeted metabonomics， with eight rats in each group. Differential metabolites （DEMs） were identified according to the standard of VIP>1.0 and P<0.05， and functional enrichment and interaction analyses of the Kyoto Encyclopedia of Genes and Genomes （KEGG） were performed to obtain the key metabolites and metabolic pathways associated with the analgesic effects of l-THP. ResultIn behavioral science， administration of both l-THP and Pre significantly improved mechanical hyperalgesia in CCI rats （P<0.01）， thus mitigating pain. Metabonomic analysis results revealed that l-THP administration corrected the aberrant metabolic profile in the spinal cord of CCI rats. Meanwhile， 53 DEMs were called back， including several classical pain biomarkers such as sphingosine-1-phosphate （S1P）， cyclic adenosine monophosphate （cAMP）， acetylcholine， and glutamate. Functional enrichment analysis of the DEMs indicated the involvement of metabolic pathways such as ferroptosis， autophagy， neuroactive ligand-receptor interactions， phospholipase D and cAMP-related signaling pathways， glutathione metabolism， and cofactor biosynthesis in mediating the effects of l-THP on the metabolic profile of the spinal cord. Further analyses on the relative metabolite abundance and metabolic pathways indicated that by significantly decreasing the relative levels of glutamate （P<0.01） and glycine （P<0.01） in the spinal cord， l-THP can promote the synthesis of reduced glutathione （GSH） and increase the ratio of reduced/oxidized GSH （P<0.05）. Additionally， it can relieve oxidative stress in the spinal cord of CCI rats and significantly reduce the acetyl-CoA level （P<0.01） to finally inhibit ferroptosis occurrence. Conclusionl-THP may exert analgesic effects by regulating multiple metabolic pathways including GSH metabolism， ferroptosis， cofactor biosynthesis， and amino acid synthesis to correct the aberrant metabolic profile in the spinal cord of CCI rats. Ferroptosis and GSH metabolism may be the key pathways for l-THP regulation， with glutamate， glycine， glutathione， and acetyl-CoA as the key metabolites.

OBJECTIVE To systematically evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists(GLP-1RA) in the renal protection of type 2 diabetes(T2DM) patients, and provide evidence for clinic. METHODS Computer retrieval of PubMed, Embase, The Cochrane Library, Clinical Trials.gov, CNKI, WanFang Data and VIP databases, and manual retrieval of the included references. Randomized controlled trials(RCTs) for T2DM using GLP-1RA alone or GLP-1RA in combination with other conventional agents(experimental group) versus conventional treatment without GLP-1RA or placebo(control group). The search period spanned from the establishment of the database to January 30, 2022. Meta-analysis of the included data was performed using RevMan 5.4 statistical software. RESULTS A total of 7 studies were included, including 7 985 cases in experimental group and 6 633 cases in control group. Meta-analysis showed that the experimental group significantly reduced the incidence of renal complex endpoint events[Z=2.17, P=0.03, RR=0.79, 95%CI(0.64, 0.98)], urinary albumin creatinine ratio[Z=11.66, P<0.00001, MD=–23.74, 95%CI(–27.73, –19.74)], incidence of new macroalbuminuria[Z=5.79, P<0.000 01, MD=0.76, 95%CI(0.69, 0.83)], hemoglobin A1c[Z=12.76, P<0.000 01, MD=–0.94, 95%CI(–1.09, –0.80)] and estimated glomerular filtration rate[P=0.0007, Z=3.39, MD=–7.37, 95%CI(–11.63, –3.10)], the differences were statistically significant. One study showed that the experimental group could significantly reduce 24-hour urinary albumin excretion rate. However, there was no significant difference in the incidence of acute renal failure between the two groups[Z=0.63, P=0.53, MD=1.13, 95%CI(0.78, 1.63)]. In terms of safety, except the incidence of hypoglycemia, the incidence of adverse reactions in the experimental group was higher than that in the control group, including diarrhea, nausea, vomiting and loss of appetite, with statistically significant differences. CONCLUSION Existing research evidence shows that the common adverse reactions of GLP-1RA are gastrointestinal reactions and can be tolerated. Compared with placebo or conventional treatment without GLP-1RA, GLP-1RA may have a protective effect on the kidney of T2DM patients, and this conclusion needs to be further verified by RCTs.