ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

To systematically analyzed the reporting status of core elements in publicly available clinical practice guideline(hereafter referred to as "guideline") protocols published domestically and internationally over the past decade, identified existing problems, and provided evidence to inform the standardized writing and publication of future guideline protocols.

ObjectiveTo establish a reliable chronic obstructive pulmonary disease (COPD) mouse model based on a self-developed multichannel automatic control system for long-term continuous cigarette smoke exposure in small animals using a novel continuous cigarette smoke exposure method, and to conduct phenotypic evaluation and analysis, thereby providing an animal experimental basis for investigating COPD pathogenesis and prevention strategies. MethodsTwenty male C57BL/6J mice aged 6 weeks were randomly and equally divided into a control group and a model group. The model group (n=10) underwent 6 h of continuous cigarette smoke exposure daily (6 cigarettes per day for 12 consecutive weeks), while the control group (n=10) received no intervention. Body weight was monitored biweekly. Post-exposure, in vivo micro-CT imaging was performed. After euthanasia, serum and bronchoalveolar lavage fluid (BALF) levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were quantified by ELISA. Lung tissues underwent H&E and Masson's trichrome staining to observe changes in lung morphology and inflammatory cell infiltration, and the mean linear intercept (MLI) was calculated, thereby comprehensively evaluating the clinical features of COPD in the mouse model. ResultsCompared with the control group, the model group showed significantly reduced body weight (P<0.01) from the fourth week. Compared with the control group, IL-6 level in the serum and BALF of the model group increased by 27.2% and 140.0%, respectively (P<0.01). TNF-α level in the serum and bronchoalveolar lavage fluid of the model group increased by 16.7% (P<0.01) and 19.3% (P<0.05), respectively. Histopathological examination revealed alveolar wall thinning, septal rupture, emphysematous bullae formation, reduced alveolar count, bronchial wall thickening with lumen narrowing, and inflammatory cell infiltration. MLI was significantly elevated (P<0.01). Masson's staining confirmed collagen deposition and bronchial remodeling. Micro-CT demonstrated localized high-density shadows exhibiting typical features of chronic bronchitis. Conclusion The self-developed device enables long-term continuous smoke exposure, and the successfully established COPD mouse model exhibits pathological features highly consistent with clinical manifestations, offering an efficient and reliable tool for COPD research.

ObjectiveTo explore the effects of Wumeiwan on liver metastasis and lung metastasis of colorectal cancer and its potential mechanism. MethodsFirstly， mice were randomized into control， low-dose （20 g·kg^-1） Wumeiwan， high-dose （40 g·kg^-1） Wumeiwan， and paclitaxel （10 mg·kg^-1） groups. Secondly， liver metastasis and lung metastasis models of colorectal cancer were established in mice. After 4 weeks of intervention， the body weight of each mouse was recorded， and the lung weight， liver weight， and survival time of mice with metastatic colorectal cancer were determined. Hematoxylin-eosin （HE） staining was employed to detect the effects of Wumeiwan on liver metastasis and lung metastasis. Real-time PCR was employed to determine the mRNA levels of M1 and M2 macrophage markers in the liver tissue. Finally， the content of M1 macrophage markers CD80 and CD86 in the liver tissue was measured by flow cytometry. ResultsCompared with the control group， Wumeiwan and paclitaxel reduced the body weight （P<0.01） and liver weight （P<0.01） and prolonged the survival of the mouse model of liver metastasis of colorectal cancer （P<0.01）. In the mouse model of lung metastasis of colorectal cancer， Wumeiwan and paclitaxel also reduced the body weight （P<0.01） and lung weight （P<0.01） and extended the survival time （P<0.01）. Histopathological results showed that compared with the control group， Wumeiwan inhibited the liver and lung metastases of colorectal cancer. Real-time PCR results showed that compared with the control group， Wumeiwan upregulated the mRNA levels of M1 macrophage markers IL-1β， IL-6， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and prostaglandin-endoperoxide synthase 2 （PTGS2） in the liver and lung tissue of mice with liver metastasis and lung metastasis of colorectal cancer （P<0.01）. Meanwhile， Wumeiwan downregulated the mRNA levels of M2 macrophage markers Arg1， CD163， and CD206 （P<0.01）. Meanwhile， the flow cytometry results showed that compared with the control group， Wumeiwan increased the content of CD86 and CD80 （P<0.01）. In addition， immunohistochemical results showed that Wumeiwan promoted the expression of CD86 and inhibited the expression of CD206 in the liver and lung tissue of mice with liver metastasis and lung metastasis. ConclusionWumeiwan can inhibit the liver metastasis and lung metastasis of colorectal cancer by promoting the M1 polarization of macrophages in the liver and lung of the model mice.

ObjectiveThis paper aims to assess the effects of Wenfei Guyuan umbilical moxibustion on the quality of life and immune function in patients with chronic obstructive pulmonary disease （COPD） in stable phase. MethodsA multi-center randomized controlled trial design was employed，and the 220 cases of patients with COPD in stable phase from three grade A class-Ⅲ hospitals were included as research objects. The patients were randomly divided into the test group and control group，with each group consisting of 110 cases. Both groups received standardized treatment of western medicine，and the test group received Wenfei Guyuan umbilical moxibustion twice weekly for 13 weeks，followed by a 26-week follow-up period. Quality of life was evaluated by using the COPD assessment test （CAT），the modified COPD patient-reported outcomes （mCOPD-PRO） measure，and the modified effectiveness satisfaction questionnaire for COPD （mESQ-COPD） before treatment，four weeks， eight weeks， and 13 weeks of the treatment period，as well as 13 weeks and 26 weeks of the follow-up period. The number of acute exacerbation cases of patients in both groups was recorded during study period to evaluate the effect of Wenfei Guyuan umbilical moxibustion on acute exacerbations. 30 cases were randomly selected in both observation group and control group. Peripheral blood samples were collected before treatment and at 13 weeks of treatment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of immunoglobulin A （IgA），immunoglobulin G （IgG），immunoglobulin M （IgM），interleukin 10 （IL-10），interleukin 17A （IL-17A），transforming growth factor β1 （TGF-β1），and tumor necrosis factor α （TNF-α）. Flow cytometry was used to detect cluster of differentiation 4 positive （CD4⁺），cluster of differentiation 8 positive （CD8⁺），T helper 17 （Th17），and Treg levels， thereby preliminarily exploring the effect of Wenfei Guyuan umbilical moxibustion on immune function. ResultsA total of 220 patients were included，with five cases dropping out. 215 cases were finally included in the per-protocol set，including 107 in the treatment group and 108 in the control group. Baseline characteristics of the first two groups before treatment were compared between the two groups. In terms of life quality evaluation， the main effect of group differences on the CAT scores was significant （F=15.108，P<0.01）. The main effects of group differences on the physical domain （F=38.807，P<0.01），psychological domain （F=38.996，P<0.01），environmental domain （F=17.436，P<0.01），and total score of mCOPD-PRO （F=41.972，P<0.01） were significant. The main effects of group difference on clinical symptoms domain of mESQ-COPD （F=81.516，P<0.01），work-life ability domain （F=36.549，P<0.001），environmental adaptation ability domain （F=22.677，P<0.01），therapeutic effect domain （F=74.055，P<0.01），and total score of mESQ-COPD （F=73.251，P<0.01） were significant. Regarding acute exacerbations，during the entire study period，as well as the treatment period and follow-up period，the observation group showed fewer patients experiencing acute exacerbations compared to the control group，but the difference between the two groups was not statistically significant. In terms of immune indicators，after 13 weeks of treatment，the levels of IgA，IgG，and IgM in the observation group were significantly better than those in the control group （P<0.05）. The level of IL-10 was significantly higher than that in the control group （P<0.05），and the levels of IL-17A，TGF-β1，and TNF-α were significantly lower than those in the control group （P<0.05）. Compared with those in the control group，the level of CD4⁺/CD8⁺ in the observation group was significantly increased （P<0.05），while the levels of CD4⁺ and Treg were slightly increased，but the difference was not statistically significant. The levels of CD8⁺，Th17，and Th17/Treg were significantly decreased （P<0.05）. ConclusionWenfei Guyuan umbilical moxibustion can improve the quality of life， and immune function in patients with COPD in stable phase. It is worth promoting in clinical practice.

To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

The Guidelines for Construction of Traditional Chinese Medicine Pharmacovigilance Systems in Medical Institutions （T/CACM 1563.2-2024） were the first special guideline in China to systematically assist medical institutions in establishing a pharmacovigilance system tailored to the characteristics of traditional Chinese medicine （TCM）. This guideline was jointly developed with 23 authoritative medical and research institutions in China， under the lead of the Institute of Basic Clinical Medicine， China Academy of Chinese Medical Sciences. The purpose of this guideline was to standardize pharmacovigilance work throughout the entire lifecycle of TCM （including research and development， marketing， and application） and to establish a four-dimensional framework of "organizational structure， institutional system， information platform， and vigilance activities". Key components included the establishment of a TCM Safety Committee， the construction of nine core systems， the development of an information platform that complies with International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use （ICH） E2B standards， alongside the risk monitoring， identification， assessment， and control during clinical trials and post-marketing phases. Therefore， this guideline filled a significant gap in the systemic standards for TCM safety management within medical institutions. Strictly adhering to domestic and international laws and regulations， the guideline compilation involved multiple rounds of expert interviews， systematic evidence integration， and broad consensus. This guideline was specified to be applicable to medical institutions at all levels， primarily addressing core issues， including the difficulty in adverse reaction identification， low reporting rates， and incomplete risk management chains due to the complex composition and diverse application of TCM. The compilation process was scientific and rigorous， ensuring alignment with current national laws and regulations， and was registered internationally. In the future， implementation will be promoted through standardized training， tiered dissemination， as well as a post-effect evaluation and dynamic revision mechanism starting two years after publication. All these aimed to enhance medical institutions' proactive capabilities in preventing and controlling TCM safety risks， ensure patient medication safety， and promote the high-quality development of TCM.