Hepatic fibrosis （HF） is an abnormal repair process that occurs after chronic liver injury. It is characterized by excessive accumulation of extracellular matrix in the liver， resulting in fibrous tissue hyperplasia， which may further develop into cirrhosis and even liver cancer. Currently， there is a lack of specific anti-HF drugs in clinical practice. Traditional Chinese medicine （TCM） has advantages in the treatment of HF， including multi-component and multi-target interventions with high safety， and can significantly delay the progression of HF. It has therefore become a current research hotspot. Nuclear factor erythroid 2-related factor 2 （Nrf2）， as a key transcription factor involved in antioxidant stress， can effectively intervene in the progression of HF by activating the expression of downstream antioxidant enzymes and detoxification genes. This article systematically reviews the mechanisms by which active components of Chinese medicine （such as flavonoids， polysaccharides， and saponins） and TCM compound prescriptions （such as Haobie Yangyin Ruanjian prescription and Biejia Xiaozheng pills） exert anti-fibrotic effects through activation of the Nrf2 signaling pathway， including enhancing antioxidant capacity， inhibiting inflammatory responses， reducing hepatocyte apoptosis， improving mitochondrial function， and inhibiting the ferroptosis pathway. In addition， this article points out the current shortcomings in research based on the Nrf2 signaling pathway and proposes corresponding suggestions to promote related studies. It also provides an important theoretical basis for the development of novel anti-HF Chinese medicine targeting Nrf2.

Digital intelligence technology is a comprehensive technical system with data as the key element and artificial intelligence as the core driving force. It provides innovative methodological support for addressing core bottlenecks in rare disease etiology research, including sample scarcity, high-dimensional datacomplexity, intricate pathogenic mechanisms, and challenges in causal validation. This paper systematically reviews the application pathways and current implementation of digital intelligence across four major stages of rare disease research, including etiological clue mining, causal inference, mechanism analysis, and clinical translation. Furthermore, it summarizes the technical strengths, existing limitations, and developmental challenges, aiming to inform optimization of the research paradigm and promote the sustainable advancement of rare disease research.

Hepatocellular carcinoma （HCC） with biliary duct tumor thrombus （BDTT） is currently not common in clinical practice and is easily misdiagnosed， and previously， it was often considered an advanced stage of the disease with a poor prognosis， making its treatment challenging. However， in-depth studies in recent years have gradually deepened our understanding of this disease， leading to significant changes in diagnostic and treatment concepts. Currently， comprehensive treatment， mainly surgery， is used for treatment， but there is still controversy over the selection of clinical treatment strategies. This article provides a detailed discussion on surgical methods and prognosis， in order to provide a reference for clinical treatment options.

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Congenital orofacial cleft, the most common birth defect in the maxillofacial region, exhibits a wide range of prognosis depending on the severity of deformity and underlying etiology. Non-syndromic congenital orofacial clefts typically present with milder deformities and more favorable treatment outcomes, whereas syndromic congenital orofacial clefts often manifest with concomitant organ abnormalities, which pose greater challenges for treatment and result in poorer prognosis. This consensus provides an elaborate classification system for varying degrees of orofacial clefts along with corresponding diagnostic and therapeutic guidelines. Results serve as a crucial resource for families to navigate prenatal screening results or make informed decisions regarding treatment options while also contributing significantly to preventing serious birth defects within the development of population.
Humans ; Cleft Lip/diagnosis* ; Cleft Palate/diagnosis* ; Consensus ; Prenatal Diagnosis ; Female

Objective To analyze the spatial distribution patterns of the potential suitable habitats for Cremastrae Pseudobulbus Pleiones Pseudobulbus,including Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe under current climatic conditions,and the factors influencing the spatial differentiation of their habitats.Methods Based on the maximum entropy(MaxEnt)model,a species distribution model was established using the screened species distribution data and environmental variable data.The factor detection and interaction detection of geographical detector were applied to quantify the factors influencing the spatial differentiation of the suitable areas.By overlaying the suitable areas with land cover types,the distribution characteristics of forest land and arable land in the potential suitable areas were quantified.Results Under the current climatic scenario,environmental variables such as solar radiation intensity,precipitation and temperature were closely related to the spatial distribution of Cremastrae Pseudobulbus Pleiones Pseudobulbus.The potential suitable areas for Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe were 2.20×106 km2,2.75×106 km2 and 7.22×105 km2,respectively.Considering land cover types,the actual possible suitable areas for Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe were 1.86×106 km2,2.20×106 km2 and 5.77×105 km2,respectively.Among these,the area of forest land was 1.17×106 km2,1.34×106 km2 and 3.67×105 km2,respectively,and the area of arable land was 6.95×105 km2,8.64×105 km2 and 2.10×105 km2,respectively.Conclusion This study can provide a basis for the protection and sustainable utilization of wild resources of the original plant materials of Cremastrae Pseudobulbus Pleiones Pseudobulbus.

Objective:To construct a nomogram model for predicting the incidence of hepatocellular carcinoma based on serum abnormal prothrombin and alpha-fetoprotein and evaluate the predictive effect.Methods:Retrospective analysis of data from 351 patients with liver disease who received treatment at the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023, including 285 males and 66 females, aged (52.9±11.9) years. Among the 351 patients, there were 229 cases (65.2%) of hepatocellular carcinoma, 87 cases (24.8%) of liver cirrhosis, and 35 cases (10.0%) of chronic hepatitis B. All patients were randomly divided into a training set ( n=245) and a testing set ( n=106) in a 7∶3 ratio without replacement sampling. The training set was used to construct the model, and the testing set was used to evaluate the model. At the same time, gender, age, disease type, and other indicators were compared between the two sets. The risk factors of hepatocellular carcinoma were analyzed by univariate and multivariate logistic regression based on the training set, and a nomogram was constructed to predict the incidence of hepatocellular carcinoma based on the multivariate results. Receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the predictive performance of nomogram, and decision curve analysis was used to evaluate the clinical applicability of the model. Results:There was no statistically significant difference in age, gender, disease type, etc. between the training and testing sets of patients (all P>0.05). Univariate logistic regression analysis showed that age, abnormal prothrombin logarithm (LnPIVKA-Ⅱ), alpha-fetoprotein logarithm (LnAFP), and diabetes were associated with hepatocellular carcinoma (all P<0.05). Multivariate logistic regression analysis showed that older age ( OR=1.07, 95% CI: 1.03-1.12), higher LnPIVKA-Ⅱ ( OR=2.97, 95% CI: 1.97-4.46), higher LnAFP ( OR=1.43, 95% CI: 1.11-1.84) and diabetes ( OR=5.17, 95% CI: 1.02-26.17) were risk factors for hepatocellular carcinoma (all P<0.05). Based on the above variables, a nomogram model for predicting the incidence of hepatocellular carcinoma was constructed. The area under the ROC curve analysis of the nomogram for predicting the incidence of hepatocellular carcinoma was 0.920 (95% CI: 0.886-0.953) in the training set and 0.934 (95% CI: 0.891-0.977) in the testing set. The calibration curve fit well with the standard curve, and the prediction was basically consistent with the actual situation. The decision curve analysis showed that the net benefit of the model was greater than 0 under most thresholds (0.1-1.0). Conclusion:The nomogram constructed based on age, LnPIVKA-Ⅱ, LnAFP and diabetes can effectively predict the incidence of hepatocellular carcinoma and has clinical applicability.

Objective To investigate the spatial distribution pattern of the suitable habitats for Codonopsis pilosula(Franch.)Nannf.and the factors influencing the spatial differentiation of its habitat under current climatic conditions in China.Methods Based on maximum entropy(MaxEnt)model,a species distribution model was established with filtered species occurrence data and environmental variable data.The geographical detector was applied to quantify the factors influencing the spatial differentiation of the suitable areas,employing both factor detection and interaction detection functionalities.Additionally,an overlay analysis with land cover types was conducted to quantify the distribution characteristics of arable land and forest land within the potential suitable areas for Codonopsis pilosula(Franch.)Nannf..Results Based on the contribution rate of environmental factors and the Jackknife method,average solar radiation intensity in December,precipitation in July,and highest temperature in December were identified as key environmental factors affecting the suitability of Codonopsis pilosula(Franch.)Nannf.habitats,which were further validated by the geographical detector.The total suitable area for Codonopsis pilosula(Franch.)Nannf.in China under current climatic conditions was approximately 4.46×106 km2,with the areas of high,moderate,and low suitability being 1.08×106 km2,1.70×106 km2,and 1.68×106 km2,respectively.After overlaying with arable and forest lands,the potentially suitable total forest area for Codonopsis pilosula(Franch.)Nannf.was 1.55×106 km2,and the arable land area was 1.63×106 km2.Conclusion This study provides reference for the optimization of cultivation areas for Codonopsis pilosula(Franch.)Nannf.and the conservation of its wild resources.