Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mechanisms of saponins from Panax japonicus(SPJ) on anxiety disorder in mice fed a high-fat diet(HFD). Fifty C57BL/6J mice were randomly divided into normal control diet(NCD) group, HFD group, and low-and high-dose SPJ groups. At week 12, six mice from the HFD group were further divided into a control group(treated with DMSO) and an exogenous fibroblast growth factor 21(FGF21) group(administered rFGF21). The anxiety-like behavior of the mice was assessed using the open field test and elevated plus maze test. Hematoxylin-eosin(HE) staining and oil red O staining were performed to observe pathological changes in the liver and adipose tissue. Glucose metabolism was evaluated through the glucose tolerance test(GTT) and insulin tolerance test(ITT). Western blot analysis was performed to detect the expression of FGF21 and its downstream-related proteins in the liver and cortex, along with the expression of brain-derived neurotrophic factor(BDNF), disks large homolog 4(DLG4), and synaptophysin(SYP) in the cortex. Real-time quantitative fluorescent PCR(qPCR) was used to detect the expression of FGF21 and its receptor genes in the liver and cortex. Immunofluorescence staining was employed to examine the expression of neuronal activator c-Fos, FGF21, and the FGF21 co-receptor β-klotho in the cerebral cortex. The results showed that SPJ significantly improved the frequency of activity in the open arms of the elevated plus maze and the central area of the open field in HFD mice, up-regulated the expression of BDNF, DLG4, and SYP, and effectively alleviated anxiety-like behaviors in HFD mice. Compared with the NCD group, HFD mice exhibited up-regulated expression of FGF21 in the liver and cerebral cortex, while the expression of fibroblast growth factor receptor 1(FGFR1) and β-klotho was significantly down-regulated, suggesting that HFD mice exhibited FGF21 resistance. SPJ markedly up-regulated the β-klotho levels in HFD mice, reversing FGF21 resistance. Further comparison with exogenously administered FGF21 revealed that SPJ activates brain cortical regions in a consistent manner, and additionally, SPJ promotes the number and colocalization of c-Fos and β-klotho positive cells in the brain cortex. In summary, SPJ effectively alleviates anxiety-like behaviors in HFD mice. Its mechanism is associated with up-regulation of β-klotho expression in the brain, reversal of FGF21 resistance, and subsequent activation of neurons in the cerebral cortex and amygdala.
Animals ; Diet, High-Fat/adverse effects* ; Fibroblast Growth Factors/genetics* ; Mice ; Male ; Panax/chemistry* ; Mice, Inbred C57BL ; Anxiety/etiology* ; Saponins/administration & dosage* ; Brain-Derived Neurotrophic Factor/genetics* ; Humans ; Liver/metabolism* ; Drugs, Chinese Herbal/administration & dosage*

Traditional Chinese medicine(TCM) decoction pieces are a core carrier for the inheritance and innovation of TCM, and their quality and safety are critical to public health and the sustainable development of the industry. Conventional quality control models, while having established a well-developed system through long-term practice, still face challenges such as relatively long inspection cycles, insufficient objectivity in characterizing complex traits, and urgent needs for improving the efficiency of integrating multidimensional quality information when confronted with the dual demands of large-scale production and precision quality control. With the rapid development of artificial intelligence, machine learning can deeply analyze multidimensional data of the morphology, spectroscopy, and chemical fingerprints of decoction pieces by constructing high-dimensional feature space analysis models, significantly improving the standardization level and decision-making efficiency of quality evaluation. This article reviews the research progress in the application of machine learning in the processing, production, and rapid quality evaluation of TCM decoction pieces. It further analyzes current challenges in technological implementation and proposes potential solutions, offering theoretical and technical references to advance the digital and intelligent transformation of the industry.
Machine Learning ; Drugs, Chinese Herbal/standards* ; Quality Control ; Medicine, Chinese Traditional/standards* ; Humans

Dysregulated RNA splicing is a well-recognized characteristic of colorectal cancer (CRC); however, its intricacies remain obscure, partly due to challenges in profiling full-length transcript variants at the single-cell level. Here, we employ high-depth long-read scRNA-seq to define the full-length transcriptome of colorectal epithelial cells in 12 CRC patients, revealing extensive isoform diversities and splicing alterations. Cancer cells exhibited increased transcript complexity, with widespread 3'-UTR shortening and reduced intron retention. Distinct splicing regulation patterns were observed between intrinsic-consensus molecular subtypes (iCMS), with iCMS3 displaying even higher splicing factor activities and more pronounced 3'-UTR shortening. Furthermore, we revealed substantial shifts in isoform usage that result in alterations of protein sequences from the same gene with distinct carcinogenic effects during tumorigenesis of CRC. Allele-specific expression analysis revealed dominant mutant allele expression in key oncogenes and tumor suppressors. Moreover, mutated PPIG was linked to widespread splicing dysregulation, and functional validation experiments confirmed its critical role in modulating RNA splicing and tumor-associated processes. Our findings highlight the transcriptomic plasticity in CRC and suggest novel candidate targets for splicing-based therapeutic strategies.
Humans ; Colorectal Neoplasms/metabolism* ; RNA Isoforms/metabolism* ; Single-Cell Analysis ; RNA Splicing ; Gene Expression Regulation, Neoplastic ; RNA, Neoplasm/metabolism* ; Transcriptome

Objective:To evaluate the clinical efficacy and safety of an antioxidant gel containing tea polyphenols combined with narrow-band ultraviolet B in the treatment of vitiligo.Methods:A single-center, randomized controlled clinical trial was conducted. From April 25 to June 27, 2024, patients with vitiligo were selected from the Department of Dermatology, Hangzhou Third People's Hospital. An open-label and researcher-blinded design was used. The patients were divided into 3 groups: a phototherapy group receiving phototherapy alone, a tea polyphenols combined group treated with an antioxidant gel containing tea polyphenols combined with phototherapy, and a positive control group treated with an antioxidant gel containing superoxide dismutase combined with phototherapy, with the treatment duration being 3 months. The efficacy was evaluated using the Vitiligo Area Scoring Index (VASI), and when the VASI was improved by ≥ 10%, the treatment would be considered effective. Changes in skin aging and skin barrier function indicators before and after treatment were assessed for 72 vitiligo lesions in the tea polyphenols combined group and for 72 lesions in the phototherapy group. Comparisons between the groups were performed using one-way analysis of variance, Fisher's exact test, chi-square test, or t test. Results:A total of 171 vitiligo patients with 307 target lesions were successfully followed up in this study, including 74 males and 97 females, and their ages ranged from 1 to 64 years. Among the 307 lesions, 95 were treated with phototherapy alone, of which 35 showed improvement, resulting in a total response rate of 36.8% and an average VASI improvement rate of 10.9%; adverse reactions occurred in 29 lesions (30.5%). Of 138 lesions treated with the antioxidant gel containing tea polyphenols combined with phototherapy, 73 showed improvement, resulting in a total response rate of 52.9% and an average VASI improvement rate of 24.0%; adverse reactions occurred in 10 lesions (7.2%). In the positive control group, 74 lesions were treated, and 40 showed improvement, resulting in a total response rate of 54.1% and an average VASI improvement rate of 18.3%; adverse reactions occurred in 5 lesions (6.8%). Compared with the phototherapy group, the tea polyphenols combined group showed a significantly increased total response rate and a VASI improvement rate (both P < 0.01), but a significantly decreased incidence rate of adverse reactions ( P < 0.001). No significant differences in the above indicators were observed between the tea polyphenols combined group and the positive control group (all P > 0.05). In addition, the changes in skin barrier function and skin aging indicators (except for wrinkle depth) before and after treatment were significantly reduced in the tea polyphenols combined group compared to the phototherapy group (all P < 0.05). After the phototherapy alone, the transepidermal water loss significantly increased ( P = 0.004), and the water content of the stratum corneum significantly decreased ( P = 0.012). However, no significant differences in skin barrier function or skin aging indicators were found between pre- and post-treatment in the tea polyphenols combined group ( P > 0.05) . Conclusion:The antioxidant gel containing tea polyphenols could effectively improve the efficacy of narrow-band ultraviolet B in the treatment of vitiligo, and alleviate skin aging and barrier damage caused by phototherapy.

Objective:To evaluate the clinical efficacy and safety of an antioxidant gel containing tea polyphenols combined with narrow-band ultraviolet B in the treatment of vitiligo.Methods:A single-center, randomized controlled clinical trial was conducted. From April 25 to June 27, 2024, patients with vitiligo were selected from the Department of Dermatology, Hangzhou Third People's Hospital. An open-label and researcher-blinded design was used. The patients were divided into 3 groups: a phototherapy group receiving phototherapy alone, a tea polyphenols combined group treated with an antioxidant gel containing tea polyphenols combined with phototherapy, and a positive control group treated with an antioxidant gel containing superoxide dismutase combined with phototherapy, with the treatment duration being 3 months. The efficacy was evaluated using the Vitiligo Area Scoring Index (VASI), and when the VASI was improved by ≥ 10%, the treatment would be considered effective. Changes in skin aging and skin barrier function indicators before and after treatment were assessed for 72 vitiligo lesions in the tea polyphenols combined group and for 72 lesions in the phototherapy group. Comparisons between the groups were performed using one-way analysis of variance, Fisher's exact test, chi-square test, or t test. Results:A total of 171 vitiligo patients with 307 target lesions were successfully followed up in this study, including 74 males and 97 females, and their ages ranged from 1 to 64 years. Among the 307 lesions, 95 were treated with phototherapy alone, of which 35 showed improvement, resulting in a total response rate of 36.8% and an average VASI improvement rate of 10.9%; adverse reactions occurred in 29 lesions (30.5%). Of 138 lesions treated with the antioxidant gel containing tea polyphenols combined with phototherapy, 73 showed improvement, resulting in a total response rate of 52.9% and an average VASI improvement rate of 24.0%; adverse reactions occurred in 10 lesions (7.2%). In the positive control group, 74 lesions were treated, and 40 showed improvement, resulting in a total response rate of 54.1% and an average VASI improvement rate of 18.3%; adverse reactions occurred in 5 lesions (6.8%). Compared with the phototherapy group, the tea polyphenols combined group showed a significantly increased total response rate and a VASI improvement rate (both P < 0.01), but a significantly decreased incidence rate of adverse reactions ( P < 0.001). No significant differences in the above indicators were observed between the tea polyphenols combined group and the positive control group (all P > 0.05). In addition, the changes in skin barrier function and skin aging indicators (except for wrinkle depth) before and after treatment were significantly reduced in the tea polyphenols combined group compared to the phototherapy group (all P < 0.05). After the phototherapy alone, the transepidermal water loss significantly increased ( P = 0.004), and the water content of the stratum corneum significantly decreased ( P = 0.012). However, no significant differences in skin barrier function or skin aging indicators were found between pre- and post-treatment in the tea polyphenols combined group ( P > 0.05) . Conclusion:The antioxidant gel containing tea polyphenols could effectively improve the efficacy of narrow-band ultraviolet B in the treatment of vitiligo, and alleviate skin aging and barrier damage caused by phototherapy.

Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and adolescents. Methods A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,China.Anthropometric indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were utilized.Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of obesity. Results We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)= 0.68;95%confidence interval(CI)= 0.59,0.78]and abdominal obesity(OR = 0.68;95%CI = 0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR = 0.31,95%CI = 0.19,0.50)or abdominal obesity(OR = 0.46,95%CI = 0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR = 2.06,95%CI = 1.09,3.91). Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood obesity.Children and adolescents with high levels of vitamin B12 and folate were less likely to be obese.

OBJECTIVE: To investigate the clinical significance of SFRP1 gene and its methylation in childhood acute lymphoblastic leukemia (ALL) . METHODS: Methylation-specific PCR (MSP) was used to detect the methylation status of SFRP1 gene in bone marrow mononuclear cells of 43 children with newly diagnosed ALL before chemotherapy (primary group) and when the bone marrow reached complete remission d 46 after induction of remission chemotherapy (remission group), the expression of SFRP1 mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR), the expression of SFRP1 protein was detected by Western blot, and clinical data of children were collected, the clinical significance of SFRP1 gene methylation in children with ALL was analyze. RESULTS: The positive rate of SFRP1 gene promoter methylation in the primary group (44.19%) was significantly higher than that in the remission group (11.63%) (χ2=11.328, P<0.05). The relative expression levels of SFRP1 mRNA and protein in bone marrow mononuclear cells of children in the primary group were significantly lower than those in the remission group (P<0.05). Promoter methylation of SFRP1 gene was associated with risk level (χ2=15.613, P=0.000) and survival of children (χ2=6.561, P=0.010) in the primary group, children with SFRP1 hypermethylation had significantly increased risk and shortened event-free survival time, but no significant difference in other clinical data. CONCLUSION Hypermethylation of SFRP1 gene promoter may be involved in the development of childhood ALL, and its hypermethylation may be associated with poor prognosis.
Child ; Humans ; Clinical Relevance ; DNA Methylation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Bone Marrow/metabolism* ; RNA, Messenger/metabolism* ; Membrane Proteins/genetics* ; Intercellular Signaling Peptides and Proteins/metabolism*

OBJECTIVE: To investigate the risk factors and prognosis of cardiovascular damage in hypereosinophilia (HE). METHODS: The clinical data of 62 patients with HE in Gansu Provincial Hospital from January 2015 to December 2020 were retrospectively analyzed, including clinical characteristics and laboratory indicators, and the influencing factors of survival and prognosis were also analyzed. RESULTS: In this study, there were 34 males and 28 females, with a median age of 53.5 (20-79) years, 35 patients without cardiovascular damage, 27 patients with cardiovascular damage, including 22 patients with abnormal electrocardiogram (ECG) (81.5%), 18 patients with abnormal echocardiography (ECHO) (66.7%), 9 patients with single ECG abnormality, 5 patients with single ECHO abnormality, and other 13 patients with multiple abnormalities. In cardiovascular damage group, peripheral white blood cell count, absolute value of eosinophils, troponin T (TNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin (IL)-4 and IL-5 levels at initial diagnosis were significantly higher than those in the non-cardiovascular damage group (P <0.01), while hemoglobin, IL-2 and interferon-γ levels were significantly lower (P <0.01). There were no significant differences in age, sex, course of disease, etiological classification, platelet count, serum creatine kinase, serum creatine kinase isoenzyme and lactate dehydrogenase between the two groups (P >0.05). The 5-year overal survival rate of patients with cardiovascular damage was 88.9%, and that of patients without cardiovascular damage was 100%, the difference was statistically significant (P =0.012). The 5-year event-free survival (EFS) rate of patients with cardiovascular damage was 59.3%, and the median time was 37 (21-52) months, while that of patients without cardiovascular damage was 80%, and the median time was 63 (51-74) months (P =0.002). Age (>60 years old), course of disease (>24 months), NT-proBNP (>3 000 pg/ml), TNT (>100 ng/L), elevated IL-4 and IL-5 were associated with EFS shortening in patients with cardiovascular damage, which were independent risk factors for EFS. CONCLUSION The EFS rate in HE patients without cardiovascular damage is significantly higher than patients with cardiovascular damage. Age, course of disease, NT-proBNP, TNT, IL-4 and IL-5 are independent risk factors affecting EFS of patients with cardiovascular damage.
Male ; Female ; Humans ; Middle Aged ; Aged ; Interleukin-4 ; Biomarkers ; Retrospective Studies ; Interleukin-5 ; Prognosis ; Risk Factors ; Eosinophilia ; Peptide Fragments ; Natriuretic Peptide, Brain

Objective:To explore the difference of the vessel and plaque characteristics, myocardial perfusion and cardiac function between patients with ischemia with non-obstructive coronary artery disease (INOCA) and obstructive coronary artery disease (CAD).Methods:From July 2021 to June 2022, 101 patients with angina were referred to dynamic computed tomography myocardial perfusion (CTP) and coronary computed tomography angiography (CCTA) and retrospectively included in our hospital. Based on the results of CTP and CCTA, patients were divided into INOCA (27 cases), moderate obstructive CAD (26 cases) and severe obstructive CAD (48 cases). The anatomical coronary artery stenosis, plaque characteristics and myocardial perfusion features of all patients were analyzed. Furthermore, left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained on full-phase reconstruction CCTA image by using Medis Suite 3.2 postprocessing software. Multigroup analysis used one way ANOVA or Kruskal Wallis H test. Results:Patients with INOCA were younger than patients with moderate and severe obstructive CAD ( P<0.001). INOCA patients (7.4%, 2/27) had lower rate of positive remodeling than both moderate (57.7%, 15/26, P<0.001) and severe obstructive CAD patients (33.3%, 16/48, P=0.017). The percentage of ischemic myocardium volume in patients with INOCA were similar with those in patients with severe CAD (all P>0.05), but significantly higher than those in patients with moderate CAD (all P<0.05). No significant difference in terms of GLS was detected between patients with INOCA [-17.4% (-21.6%, -11.6%)] and severe CAD [-17.6% (-21.9%, -14.8%), P=0.536], however, patients both with INOCA and severe CAD also had higher GLS than patients with moderate obstructive CAD [-22.3% (-29.8%, -19.0%), all P<0.05]. Conclusions:Based on"one-stop-shop"CTP combined with CCTA imaging, early cardiac functional changes including abnormal myocardial perfusion and myocardial strain in INOCA patients were similar to those in patients with severe obstructive CAD and more severe than those in patients with moderate obstructive CAD.

OBJECTIVE: To investigate the phenotypes and gene frequencies of Kell blood group system K antigen and Rh blood group system D antigen in Xinjiang, and summarize and understand the distribution of Kell(K) blood type and Rh(D) blood type in this area. METHODS: A total of 12 840 patients who met the inclusion criteria during physical examination and treatment in our hospital and 18 medical institutions in our district from January 1, 2019 to December 31, 2019 were collected for identification of Kell blood group system K antigen and Rh blood group System D antigen, and the distribution of K and D blood groups in different regions, genders and nationalities were investigated and statistically analyzed. RESULTS: The proportion of K positive in the samples was 1.39%, the highest was 1.91% in southern Xinjiang, and the lowest was 1.03% in northern Xinjiang(P<0.01). The proportion of Rh(D) negative samples was 2.75% and the gene frequency was 16.64%. The proportion of Rh(D) negative samples was 4.03% and the gene frequency was 20.10% in southern Xinjiang, followed by eastern Xinjiang and the lowest in northern Xinjiang (P<0.01). The frequency of K antigen in Uygur nationality was the highest, reaching 2.16%, Kirgiz 1.54%, and the distribution trend of D/d antigen was similar to that of K antigen. Among women, the K positive frequency of Kazak nationality was slightly higher than that of Mongolian nationality. The highest proportion of K positive in Uygur women was 2.38%, which was higher than that in Uygur men (1.86%). The frequency of d phenotype in Kazak women was 3.15%, which was higher than that in Kirgiz （2.89%） (P<0.01). CONCLUSION The distributions of Kell(K) and Rh(D) blood groups in northern and southern Xinjiang and eastern Xinjiang had its own unique characteristics and differences. There are significant differences in blood group distribution among different ethnic groups and gender groups. In the future, k antigen detection can be included to further improve the investigation on the distribution of Kell blood group system in this region.
Female ; Humans ; Male ; Asian People ; China ; Ethnicity ; Gene Frequency ; Kell Blood-Group System/genetics* ; Rh-Hr Blood-Group System/genetics*