Objective To determine the molecular mechanism of Yuchang granule (YCG) against ulcerative colitis （UC） by network pharmacology-based approach combined with molecular docking. Methods TCMSP and HIT database were utilized to search the active components and potential targets of YCG. The effective targets of UC were obtained by GeneCards, CTD, and DisGeNET databases. Venn Diagram was exploited to receive common targets of YCG and UC. Network maps of the TCM of YCG-active component-common targets were constructed by the Cytoscape software to gain key active components. Protein-protein interaction （PPI） of common targets was constructed by the STRING database obtaining core common targets. The mechanism and therapeutic effects of YCG on UC were explored via gene ontology （GO） and the biological pathway （KEGG） enrichment analyses. Molecular docking technology was carried out to verify the combination of core active components with key common targets. Results 98 active components and 237 potential targets were sieved from YCG, and 1061 effective targets were screened from UC. 94 common targets of YCG and UC were regarded as potential therapeutic targets. Bioinformatics analysis revealed that quercetin, luteolin, β-quebrachol, stigmasterol, and kaempferol may be the potential candidate agents. Tumor necrosis factor （TNF）, serine/threonine-protein kinase （AKT1）, tumor protein p53 （TP53）, interleukin-6 （IL-6） and IL-1β could become potential therapeutic targets. KEGG showed pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and IL-17 signaling pathway might play an important role in YCG against UC. Molecular docking results showed that quercetin combined well with TNF, AKT1, and TP53. And stigmasterol did well with AKT1. Conclusion This study comprehensively illustrated the potential candidate agents, potential therapeutic targets, and pathways of YCG against UC. It also illustrated that YCG could act on multiple targets through multi-pathway treating UC.

Objective: To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention. Methods: From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated. Results: Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group. Conclusion Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.

BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

BACKGROUND:Streptococcus mutans is an important pathogen of dental caries,and timely detection of its levels is of great significance for early detection and treatment of dental caries. OBJECTIVE:To evaluate the effect of loop-mediated isothermal amplification(FTA-LAMP)direct extraction of Streptococcus mutans DNA. METHODS:(1)Bacterial suspensions containing ATCC standard strains(Streptococcus mutans)were prepared and inoculated into the brain-heart leachate medium.After mixed thoroughly,the mixture was then diluted in a 10-fold gradient into seven concentrations(4.2×107,4.2×106,4.2×105,4.2×104,4.2×103,4.2×102,4.2×10 CFU/mL),two parallel controls were made for each dilution level,and sterile water was used as a blank control.(2)The DNA of Streptococcus mutans was extracted using FTA Elute card,boiling method,kit extraction and lysate extraction methods separately and then amplified using LAMP technology was amplified.A specificity test was also performed to compare the differences between the four DNA extraction methods.RESULTS AND CONCLUSION:The DNA extracted by all four methods met the requirements for LAMP amplification.Specificity test results showed that only Streptococcus mutans could specifically amplify the target gene.The detection limit value of the DNA concentration was 4.2×103 CFU/mL for the lysate method,4.2×104 CFU/mL for the FTA Elute card extraction method,4.2×106 CFU/mL for the kit extraction method,and 4.2×107 CFU/mL for the boiling method.In the other aspects of the four extraction methods,the kit extraction method had the highest experimental cost,number of steps and time;the other three methods had the same number of steps,with the FTA Elute card method requiring the least amount of instruments,the boiling method having the lowest single cost,and the lysate extraction method taking the least amount of time.Only a small amount of bacteria were needed for successful extraction using both the FTA Elute card and lysate extraction methods.Compared with the FTA Elute card method,the lysate extraction method was superior in terms of time,but it had a high single cost and required more equipment.To conclude,the FTA-LAMP technology established in this study has the advantages of ease of operation,high specificity,high sensitivity,and visualization,which is expected to be a new way for efficient extraction and detection of Streptococcus mutans.

ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

OBJECTIVES: Keloids are fibrotic skin disorders characterized by excessive collagen deposition and a high recurrence rate, closely associated with inflammatory mediators. However, existing epidemiological studies are limited by confounding factors and reverse causality, making it difficult to establish causation. This study aims to investigate the causal relationship between circulating cytokines and keloids using Mendelian randomization analysis. METHODS: Significant single nucleotide polymorphisms (SNPs) associated with circulating cytokines (exposures) and keloids (outcomes) were extracted from genome-wide association study (GWAS) summary datasets. Eligible SNPs were selected as instrumental variables (IVs). Exposure data were derived from a cytokine GWAS including 8 293 Finnish participants, and outcome data from a keloid GWAS based on the UK Biobank. The inverse-variance weighted (IVW) method served as the primary analytical approach to estimate causal effects, supplemented by weighted median (WME), MR-Egger regression, and other sensitivity analyses. Horizontal pleiotropy was assessed using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test, while Cochran's Q test evaluated heterogeneity. Leave-one-out analysis was used to verify robustness and consistency. A reverse MR analysis was also conducted, with keloid as the exposure and cytokines as outcomes, to rule out reverse causation. RESULTS: IVW analysis identified significant positive causal associations between two cytokines and keloids-macrophage migration inhibitory factor (MIF) [odds ratio (OR)=2.081, 95% confidence interval (CI) 1.219 to 3.552, P=0.007] and monocyte chemoattractant protein-1 (MCP-1) (OR=1.673, 95% CI 1.036 to 2.701, P=0.035). Conversely, stem cell factor (SCF) showed a negative causal relationship with keloids (OR=0.518, 95% CI 0.269 to 0.998, P=0.049). Results from the MR-Egger and weighted median analyses were consistent with IVW findings. No evidence of horizontal pleiotropy was observed (P>0.05). Except for interleukin-6 (P=0.014), no heterogeneity was detected in other cytokines. Leave-one-out analysis further confirmed the robustness of the causal associations. In reverse MR analysis, keloids were causally related only to β-nerve growth factor (beta-NGF) (OR=1.048, 95% CI 1.002 to 1.095, P=0.039), with no heterogeneity or pleiotropy detected in most cytokines (P>0.05). CONCLUSIONS MIF and MCP-1 exhibit positive causal associations with keloid formation, while SCF shows a negative causal relationship. These findings provide new evidence for the causal involvement of inflammatory cytokines in keloid pathogenesis and offer potential molecular targets for developing novel keloid therapies.
Humans ; Keloid/blood* ; Mendelian Randomization Analysis ; Cytokines/genetics* ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; Chemokine CCL2/genetics* ; Interleukin-6/genetics* ; Macrophage Migration-Inhibitory Factors/genetics* ; Male ; Stem Cell Factor/blood* ; Female ; Intramolecular Oxidoreductases

Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Integrative Medicine ; Drugs, Chinese Herbal/therapeutic use* ; Practice Guidelines as Topic