The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

ObjectiveTo investigate the prognostic role of radiotherapy in women aged 70 years or older with breast cancer. MethodsA total of 311 women aged 70 years or older with breast cancer undergoing breast-conserving surgery in the Second Affiliated Hospital of Nanchang University between February 28， 2011 and February 28， 2021， were divided into two groups： 183 patients in the control group were given postoperative radiotherapy， and 128 patients in the case group were not treated by radiotherapy. The nonparametric Mann-Whitney U test or χ² test was used to compare the general clinicopathological data of the two groups， the Kaplan-Meier method and log-rank test to analyze the disease-free survival （DFS） and overall survival （OS）， multivariate Cox proportional hazards regression model to examine the factors affecting DFS and OS. Additional subgroup analysis was performed. ResultsThere were no statistically significant differences between the control and case groups in age， T-stage， N-stage， tumor clinical stage， estrogen receptor （ER）， progesterone receptor （PR） and human epidermal growth factor receptor type 2 （HER2） statuses， Ki-67， tumor histological grade， tumor pathological type， and whether they received adjuvant chemotherapy or postoperative endocrine therapy （all P > 0.05）. The median follow-up was 110.0 （95%CI： 98.9， 121.1） months for the control group and 93.0 （95% CI： 86.1， 100.0） months for the case group. Differences between the two groups in DFS rate were significant （92.9% vs. 85.2%， P = 0.024）， but in OS rate insignificant （92.3% vs. 88.3%， P=0.199）. Multivariate Cox proportional hazards regression analysis showed that T-stage， N-stage （N2 and N3）， HER2 status， Ki-67， tumor histological grade （grade Ⅱ and Ⅲ）， and no radiotherapy were independent risk factors for DFS in elderly breast cancer patients （all P < 0.05）， while ER status was an independent protective factor （P < 0.05）. The independent risk factors for OS in elderly breast cancer patients included tumor stage， N-stage （N2 and N3）， HER2 status， and Ki-67 （all P < 0.05）， and ER status was an independent protective factor （P < 0.05）. Subgroup analysis revealed that in elderly hormone receptor （HR）-negative breast cancer patients， the median follow-ups of the control and case groups were 123.0 （95% CI： 116.8， 129.2） months and 88.0 （95% CI： 75.2， 100.8） months， respectively， with a statistically significant difference both in DFS （91.3% vs. 68.6%， P=0.008） and OS rates （89.1% vs. 71.4%， P=0.027）. ConclusionsPost-breast-conserving radiotherapy provides a limited survival benefit in the overall elderly breast cancer patients， but a significant survival benefit in the elderly HR-negative breast cancer patients， which suggests the need for a prospective randomized controlled trial of a stratified step-down strategy for radiotherapy in elderly breast cancer patients.

AIM: To investigate the efficacy of Yangyin Yiqi Decoction combined with polyethylene glycol eye drops on dry eye disease after cataract surgery and its effect on inflammatory factors in tears.METHODS:Prospective study. A total of 104 patients(104 eyes)with dry eye disease after cataract surgery admitted to our hospital from April 2022 to March 2024 were selected and randomly divided into two groups: 52 cases(52 eyes)in the control group were treated with polyethylene glycol eye drops; 52 cases(52 eyes)in the combined group were treated with Yangyin Yiqi Decoction combined with polyethylene glycol eye drops. The dry eye symptom score, tear film stability index, tear inflammatory factor level, ocular surface disease index score(OSDI)and clinical efficacy of the two groups were compared before and after treatment.RESULTS:There were 6 cases(6 eyes)lost to follow-up, and 3 cases(3 eyes)were lost to follow-up in each group, with a loss to follow-up rate of 5.8%. The total effective rate of treatment in the combination group was significantly higher than that in the control group(94% vs 80%, P=0.037), and the Schirmer I test(SIt)and tear film break-up time(BUT)were higher than those in the control group(all P<0.05), and the dry eye symptom score, corneal fluorescein staining(FL)score, IL-1β, TNF-α, hs-CRP levels in tears and OSDI score were lower than those in the control group(all P<0.05).CONCLUSION:The combination of Yangyin Yiqi Decoction and polyethylene glycol eye drops provides an effective treatment plan for patients with dry eye disease after cataract surgery. It can effectively alleviate dry eye symptoms, reduce eye discomfort, improve tear film stability and ocular surface status, and reduce inflammatory factors in tears.

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

OBJECTIVES: To investigate the clinical features and prognosis of children with non-Down-syndrome-related acute megakaryoblastic leukemia (non-DS-AMKL). METHODS: A retrospective analysis was conducted on the medical data of 17 children with non-DS-AMKL who were admitted to Children's Hospital of The First Affiliated Hospital of Zhengzhou University from January 2013 to December 2023, and their clinical features, treatment, and prognosis were summarized. RESULTS: Among the 17 children with non-DS-AMKL, there were 8 boys and 9 girls. Fourteen patients had an onset age of less than 36 months, with a median age of 21 months (range:13-145 months). Immunophenotyping results showed that 16 children were positive for CD61 and 13 were positive for CD41. The karyotype analysis was performed on 16 children, with normal karyotype in 6 children and abnormal karyotype in 9 children, among whom 5 had complex karyotype and 1 had no mitotic figure. Detected fusion genes included EVI1, NUP98-KDM5A, KDM5A-MIS18BP1, C22orf34-BRD1, WT1, and MLL-AF9. Genetic alterations included TET2, D7S486 deletion (suggesting 7q-), CSF1R deletion, and PIM1. All 17 children received chemotherapy, among whom 16 (94%) achieved complete remission after one course of induction therapy, and 1 child underwent hematopoietic stem cell transplantation (HSCT) and remained alive and disease-free. Of all children, 7 experienced recurrence, among whom 1 child received HSCT and died of graft-versus-host disease. At the last follow-up, six patients remained alive and disease-free. CONCLUSIONS Non-DS-AMKL primarily occurs in children between 1 and 3 years of age. The patients with this disorder have a high incidence rate of chromosomal abnormalities, with complex karyotypes in most patients. Some patients harbor fusion genes or gene mutations. Although the initial remission rate is high, the long-term survival rate remains low.
Humans ; Male ; Female ; Leukemia, Megakaryoblastic, Acute/etiology* ; Child, Preschool ; Infant ; Child ; Retrospective Studies ; Prognosis ; Down Syndrome/complications*

OBJECTIVE: To explore the effect of evidence-based standardized procedures (SOP) on urinary incontinence management in patients with radical prostatectomy. METHODS: Sixty-three patients who underwent radical prostatectomy from October 2022 to September 2023 were included in the control group. And 63 patients who underwent radical prostatectomy from October 2023 to September 2024 were included in the observation group. The patients in the control group received routine perioperative care. As an addition, the SOP on urinary incontinence management was performed in the patients of observation group. The incidence of urinary incontinence, severity of urinary incontinence (1h urine pad test), quality of life (Incontinence Quality of Life Questionnaire) and comfort level (General Comfort Question) of the two groups were compared after 3 and 6 months of surgery. RESULTS: The incidence of urinary incontinence at 3 and 6 months after operation in the observation group was 36.51% and 19.05%, respectively, which were lower than those (53.97% and 38.10%) of the control group, respectively. And the incidence rates of the two groups decreased significantly (P<0.05).The score of life quality after 3 months of operation was (56.17±12.75) in the control group, which was lower than that (70.41±14.50) of the observation group. The 3-month postoperative comfort score was (52.73±11.26) in the control group and (63.49±13.52) in the observation group. The 6-month postoperative incontinence quality of life score was (64.70±11.38) in the control group and (85.41±12.04) in the observation group. And the 6-month postoperative comfort score was (60.96±8.04) in the control group and (83.49±12.04) in the observation group. The quality of life and comfort scores of the two groups 6 months after operation were significantly improved than those 3 months after operation, and the improvement of the observation group was more obvious than that of the control group (P<0.05). There were significant differences in the degree of urinary incontinence between the two groups at 3 months and 6 months after operation (P<0.05). CONCLUSION SOP management for the patients underwent radical prostatectomy can be an effective method for reducing the incidence of postoperative urinary incontinence, which promotes the recovery of postoperative urinary control.
Humans ; Prostatectomy/adverse effects* ; Male ; Urinary Incontinence/therapy* ; Quality of Life ; Surveys and Questionnaires ; Middle Aged ; Postoperative Complications/prevention & control* ; Aged

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.
Lupus Erythematosus, Systemic/immunology* ; Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Animals

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.