OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

ObjectiveChronic atrophic gastritis (CAG) is usually diagnosed by gastroscopy and histopathological biopsy. These procedures remain the reference standard, but their invasive nature and resource requirements may limit their use in large-scale population screening and repeated follow-up. A convenient and reproducible method for noninvasive auxiliary screening may help identify individuals who require further endoscopic assessment. Fingertip photoplethysmography (PPG) provides a noninvasive recording of peripheral pulse waves and allows harmonic features to be extracted from the signal. In this study, the so-called meridian-related variables were defined as PPG-derived harmonic parameters labelled according to meridian nomenclature, rather than as direct measurements of meridian physiology. This study aimed to compare these harmonic parameters between patients with CAG and non-CAG controls, identify parameters that remained different after age adjustment, and develop a multivariable model for noninvasive auxiliary screening and pre-endoscopic risk stratification of CAG. MethodsA total of 343 participants were included, comprising 171 patients with CAG and 172 non-CAG controls. CAG diagnosis was established using gastroscopy and histopathology as the reference standard. Fingertip PPG signals were collected using a PPG-based pulse acquisition device. Eight PPG-derived harmonic parameters labelled according to meridian nomenclature were extracted for analysis. Between-group differences were first assessed using nonparametric tests. Age-adjusted analyses were then performed to reduce potential confounding by age. The false discovery rate (FDR) method was applied for multiple-comparison correction. A multivariable logistic regression model integrating age and multiple harmonic parameters was constructed. Model performance was evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Internal validation performance was assessed using stratified five-fold cross-validation and bootstrap optimism correction. Threshold performance was examined using both a high-specificity strategy and a Youden index-based cutoff. Decision curve analysis was used to evaluate the model’s net clinical benefit across a range of threshold probabilities. ResultsAll eight harmonic parameters were non-normally distributed. In the univariate analysis, the stomach-labelled harmonic parameter (ST), bladder-labelled harmonic parameter (BL), and liver-labelled harmonic parameter (LR) differed between the CAG and non-CAG groups. After age adjustment and FDR correction, only ST and BL remained statistically significant. Compared with non-CAG controls, patients with CAG showed higher ST values and lower BL values. This finding indicates an associated differential harmonic pattern that was not fully explained by age distribution. However, the discriminative ability of a single harmonic parameter was limited. The best-performing single indicator was ST, with an AUC of 0.652 (95% CI: 0.595-0.707). The multivariable model integrating age and multiple harmonic parameters achieved an AUC of 0.791 (95% CI: 0.743-0.835), representing an improvement of 0.139 over ST alone. In internal validation, stratified five-fold cross-validation yielded a mean AUC of 0.753 (95% CI: 0.715-0.781), and the bootstrap optimism-corrected AUC was 0.748. These results suggest that the model retained moderate discriminative performance after internal validation.At a specificity of at least 95%, the model achieved a sensitivity of only 40.4% (95% CI: 25.7%-49.7%). This high-specificity cutoff may be suboptimal as the preferred threshold for an initial screening setting because of the potential risk of missed CAG cases. The Youden index-based optimal cutoff was 0.419, corresponding to a sensitivity of 80.7% and a specificity of 62.8%. This threshold may better match the practical aim of noninvasive auxiliary screening, where sensitivity is usually prioritized to reduce missed cases. Decision curve analysis showed that, within a threshold probability range of 10%-55%, the model provided higher net clinical benefit than the reference strategies of recommending gastroscopy for all participants or for none. ConclusionPatients with CAG showed associated harmonic differences in fingertip PPG-derived features, mainly characterized by higher ST and lower BL values after age adjustment and FDR correction. Compared with a single harmonic parameter, the multivariable model showed better overall discrimination and retained moderate internal validation performance. These findings suggest that PPG-derived harmonic parameters labelled according to meridian nomenclature may provide auxiliary information for noninvasive auxiliary screening and front-line triage before gastroscopic confirmation in CAG. The present results support further validation rather than immediate clinical implementation. External validation in independent, multicenter, and preferably prospective screening cohorts is needed to assess the model’s generalizability, screening performance, and potential clinical utility.

ObjectiveChronic atrophic gastritis (CAG) is usually diagnosed by gastroscopy and histopathological biopsy. These procedures remain the reference standard, but their invasive nature and resource requirements may limit their use in large-scale population screening and repeated follow-up. A convenient and reproducible method for noninvasive auxiliary screening may help identify individuals who require further endoscopic assessment. Fingertip photoplethysmography (PPG) provides a noninvasive recording of peripheral pulse waves and allows harmonic features to be extracted from the signal. In this study, the so-called meridian-related variables were defined as PPG-derived harmonic parameters labelled according to meridian nomenclature, rather than as direct measurements of meridian physiology. This study aimed to compare these harmonic parameters between patients with CAG and non-CAG controls, identify parameters that remained different after age adjustment, and develop a multivariable model for noninvasive auxiliary screening and pre-endoscopic risk stratification of CAG. MethodsA total of 343 participants were included, comprising 171 patients with CAG and 172 non-CAG controls. CAG diagnosis was established using gastroscopy and histopathology as the reference standard. Fingertip PPG signals were collected using a PPG-based pulse acquisition device. Eight PPG-derived harmonic parameters labelled according to meridian nomenclature were extracted for analysis. Between-group differences were first assessed using nonparametric tests. Age-adjusted analyses were then performed to reduce potential confounding by age. The false discovery rate (FDR) method was applied for multiple-comparison correction. A multivariable logistic regression model integrating age and multiple harmonic parameters was constructed. Model performance was evaluated using receiver operating characteristic (ROC) analysis and the area under the curve (AUC). Internal validation performance was assessed using stratified five-fold cross-validation and bootstrap optimism correction. Threshold performance was examined using both a high-specificity strategy and a Youden index-based cutoff. Decision curve analysis was used to evaluate the model’s net clinical benefit across a range of threshold probabilities. ResultsAll eight harmonic parameters were non-normally distributed. In the univariate analysis, the stomach-labelled harmonic parameter (ST), bladder-labelled harmonic parameter (BL), and liver-labelled harmonic parameter (LR) differed between the CAG and non-CAG groups. After age adjustment and FDR correction, only ST and BL remained statistically significant. Compared with non-CAG controls, patients with CAG showed higher ST values and lower BL values. This finding indicates an associated differential harmonic pattern that was not fully explained by age distribution. However, the discriminative ability of a single harmonic parameter was limited. The best-performing single indicator was ST, with an AUC of 0.652 (95% CI: 0.595-0.707). The multivariable model integrating age and multiple harmonic parameters achieved an AUC of 0.791 (95% CI: 0.743-0.835), representing an improvement of 0.139 over ST alone. In internal validation, stratified five-fold cross-validation yielded a mean AUC of 0.753 (95% CI: 0.715-0.781), and the bootstrap optimism-corrected AUC was 0.748. These results suggest that the model retained moderate discriminative performance after internal validation.At a specificity of at least 95%, the model achieved a sensitivity of only 40.4% (95% CI: 25.7%-49.7%). This high-specificity cutoff may be suboptimal as the preferred threshold for an initial screening setting because of the potential risk of missed CAG cases. The Youden index-based optimal cutoff was 0.419, corresponding to a sensitivity of 80.7% and a specificity of 62.8%. This threshold may better match the practical aim of noninvasive auxiliary screening, where sensitivity is usually prioritized to reduce missed cases. Decision curve analysis showed that, within a threshold probability range of 10%-55%, the model provided higher net clinical benefit than the reference strategies of recommending gastroscopy for all participants or for none. ConclusionPatients with CAG showed associated harmonic differences in fingertip PPG-derived features, mainly characterized by higher ST and lower BL values after age adjustment and FDR correction. Compared with a single harmonic parameter, the multivariable model showed better overall discrimination and retained moderate internal validation performance. These findings suggest that PPG-derived harmonic parameters labelled according to meridian nomenclature may provide auxiliary information for noninvasive auxiliary screening and front-line triage before gastroscopic confirmation in CAG. The present results support further validation rather than immediate clinical implementation. External validation in independent, multicenter, and preferably prospective screening cohorts is needed to assess the model’s generalizability, screening performance, and potential clinical utility.

This study explores the diagnosis and treatment of needle knife therapy for ankylosing spondylitis (AS) at middle and advanced stage based on the theory of meridian tendons, from a holistic perspective and syndrome differentiation. The treatment strategy includes "harmonizing yin and yang" to address root causes and "tendons-based release" to harmonize qi and blood, with the "tendons nodule points" as the core acupoint selection criterion. Based on this approach, the study systematically elaborates on two needle knife methods for AS: "governor vessel bone-piercing technique" and "below-the-umbilicus release technique", covering indications, acupoint location, and procedures. Clinical case examples are provided to enrich needle knife therapy guided by the theory of meridian tendons, offering insights for clinical and research work on AS.
Humans ; Acupuncture Points ; Acupuncture Therapy/methods* ; Meridians ; Spondylitis, Ankylosing/physiopathology* ; Tendons/physiopathology*

BACKGROUND: The combination of immune checkpoint inhibitors and chemotherapy (ICI + Chemo) shows promise in treatment of recurrent or metastatic nasopharyngeal carcinoma (RM-NPC), but some patients received limited benefit and the prognostic factors of the treatments remain unclear. Furthermore, ICIs efficacy in subsequent treatments needs further evaluation. METHODS: A systematic search on PubMed, Embase, the Cochrane Library, and major conference proceedings was conducted to identify relevant studies for meta-analysis. The study was designed to compare ICI + Chemo with chemotherapy in first-line treatment and identify efficacy predictors, and to evaluate ICIs alone in subsequent-line treatment for RM-NPC, with a focus on progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (AEs). RESULTS: Fifteen trials involving 1928 patients were included. Three trials compared ICI + Chemo with chemotherapy as a first-line treatment, while 12 trials evaluated ICIs alone in subsequent-line treatment of RM-NPC patients. First-line ICI + Chemo showed superior PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.43-0.63; P <0.001) and ORR (risk ratio [RR] = 1.14, 95% CI, 1.05-1.24; P <0.001) compared to chemotherapy, without increased AEs (RR = 1.01, 95% CI, 0.99-1.03; P = 0.481). Neither programmed death-ligand 1 (PD-L1) nor other factors predicted the efficacy of ICI + Chemo vs . chemotherapy. Subsequent-line ICIs alone had a median PFS of 4.12 months (95% CI, 2.93-5.31 months), an ORR of 24% (95% CI, 20-28%), with grade 1-5/grade 3-5 AEs at 79%/14%. However, ICIs alone were associated with significantly shorter PFS (HR = 1.31, 95% CI, 1.01-1.68; P = 0.040) than chemotherapy alone. CONCLUSIONS ICI + Chemo confers superior survival benefits compared to chemotherapy in first-line RM-NPC treatment, independent of PD-L1 expression or other factors. However, ICIs alone demonstrate a manageable safety profile but do not surpass chemotherapy in efficacy for subsequent-line treatment.
Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Nasopharyngeal Carcinoma/drug therapy* ; Nasopharyngeal Neoplasms/drug therapy* ; Neoplasm Recurrence, Local/drug therapy*

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

Dendrobium officinale(DO) is a traditional Chinese medicinal and edible plant, while it is critically endangered worldwide. This article, primarily based on the original research findings of the author's team and available articles, provides a comprehensive overview of the factors contributing to the endangerment of DO and the key technologies for the conservation, efficient cultivation, and value-added utilization of this plant. The scarcity of wild populations, low seed-setting rates, lack of endosperm in seeds, and the need for symbiosis with endophytic fungi for seed germination under natural conditions are identified as the primary causes for the rarity and endangerment of DO. Artificial seed production and tissue culture are highlighted as key technologies for alleviating the endangered status. The physiological and ecological mechanisms underlying the adaptation of DO to epiphytic growth are explored, and it is proposed that breaking the coupling of high temperature and high humidity is essential for preventing southern blight, a devastating affliction of DO. The roles of endophytic fungi in promoting the growth, improving the quality, and enhancing the stress resistance of DO are discussed. Furthermore, the integration of variety breeding, environment selection, and co-culture with endophytic fungi is emphasized as a crucial approach for efficient cultivation. The value-added applications of DO in pharmaceuticals, health foods, food products, and daily chemicals-particularly in the food and daily chemical industries-are presented as key drivers for a 10-billion-RMB-level industry. This systematic review offers valuable insights for the further development, utilization, and industrialization of DO resources, as well as for the broader application of conservation strategies for other rare and endangered plant species.
Dendrobium/microbiology* ; Endangered Species ; Seeds/microbiology* ; Fungi/physiology*