ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

This study aims to investigate the potential effect of the water extract of fresh Rehmanniae Radix on hypercholesterolemia in mice that was induced by a high-fat and high-cholesterol diet and explore its possible mechanism from bile acid reabsorption. Male C57BL/6 mice were randomly assigned into the following groups: control, model, low-and high-dose(4 and 8 g·kg~(-1), respectively) fresh Rehmanniae Radix, and positive drug(simvastatin, 0.05 g·kg~(-1)). Other groups except the control group were fed with a high-fat and high-cholesterol diet for 6 consecutive weeks to induce hypercholesterolemia. From the 6th week, mice were administrated with corresponding drugs daily via gavage for additional 6 weeks, while continuing to be fed with a high-fat and high-cholesterol diet. Serum levels of total cholesterol(TC), triglycerides(TG), low density lipoprotein-cholesterol(LDL-c), high density lipoprotein-cholesterol(HDL-c), and total bile acid(TBA), as well as liver TC and TG levels and fecal TBA level, were determined by commercial assay kits. Hematoxylin-eosin(HE) staining, oil red O staining, and transmission electron microscopy were performed to observe the pathological changes in the liver. Three livers samples were randomly selected from each of the control, model, and high-dose fresh Rehmanniae Radix groups for high-throughput transcriptome sequencing. Differentially expressed genes were mined and KEGG pathway enrichment analysis was performed to predict the key pathways and target genes of the water extract of fresh Rehmanniae Radix in the treatment of hypercholesterolemia. RT-qPCR was employed to measure the mRNA levels of cholesterol 7α-hydroxylase(CYP7A1) and cholesterol 27α-hydroxylase(CYP27A1) in the liver. Western blot was employed to determine the protein levels of CYP7A1 and CYP27A1 in the liver as well as farnesoid X receptor(FXR), apical sodium-dependent bile acid transporter(ASBT), and ileum bile acid-binding protein(I-BABP) in the ileum. The results showed that the water extract of fresh Rehmanniae Radix significantly lowered the levels of TC and TG in the serum and liver, as well as the level of LDL-c in the serum. Conversely, it elevated the level of HDL-c in the serum and TBA in feces. No significant difference was observed in the level of TBA in the serum among groups. HE staining, oil red O staining, and transmission electron microscopy showed that the water extract reduced the accumulation of lipid droplets in the liver. Further mechanism studies revealed that the water extract of fresh Rehmanniae Radix significantly down-regulated the protein levels of FXR and bile acid reabsorption-related proteins ASBT and I-BABP. Additionally, it enhanced CYP7A1 and CYP27A1, the key enzymes involved in bile acid synthesis. Therefore, it is hypothesized that the water extract of fresh Rehmanniae Radix may exert an anti-hypercholesterolemic effect by regulating FXR/ASBT/I-BABP signaling, inhibiting bile acid reabsorption, and increasing bile acid excretion, thus facilitating the conversion of cholesterol to bile acids.
Animals ; Male ; Bile Acids and Salts/metabolism* ; Mice, Inbred C57BL ; Mice ; Diet, High-Fat/adverse effects* ; Cholesterol/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Hypercholesterolemia/genetics* ; Receptors, Cytoplasmic and Nuclear/genetics* ; Rehmannia/chemistry* ; Liver/drug effects* ; Humans ; Cholesterol 7-alpha-Hydroxylase/genetics* ; Plant Extracts

To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry* ; Starch/chemistry* ; Multivariate Analysis ; Water/chemistry* ; Terpenes/analysis* ; Plant Roots/chemistry* ; Plant Tubers/chemistry* ; Drugs, Chinese Herbal/chemistry*

Eight amide alkaloids(1-8) were isolated from the 70% ethanol extract of Cannabis Fructus using silica gel column chromatography, MCI column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). Their structures were identified as hempspiramide A(1), N-[(4-hydroxyphenyl)ethyl]formamide(2), N-acetyltyramide(3), N-trans-p-coumaroyltyramine(4), N-trans-caffeoyltyramine(5), N-trans-feruloyltyramine(6), N-cis-p-coumaroyltyramine(7), N-cis-feruloyltyramine(8) by using spectroscopic methods such as NMR and MS. Among these compounds, compound 1 was a new amide alkaloid, while compounds 2 and 3 were isolated from Cannabis Fructus for the first time. Some of the isolates were assayed for their α-glucosidase inhibitory activity. Compounds 5-7 displayed significant inhibitory activity against α-glucosidase with IC_(50) values ranging from 1.07 to 4.63 μmol·L~(-1).
Cannabis/chemistry* ; Alkaloids/pharmacology* ; Amides/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Fruit/chemistry* ; Molecular Structure ; alpha-Glucosidases/chemistry* ; Chromatography, High Pressure Liquid

This study established the HPLC fingerprints and a multi-component content determination method for Bidens pilosa var. radiata and B. pilosa and conducted comprehensive evaluation by integrating fingerprint similarity comparison, cluster analysis(CA), and principal component analysis(PCA), aiming to provide a reference for the establishment of quality standards for Bidentis Herba. HPLC was launched on an Agilent Poroshell 120 EC-C_(18) chromatographic column(4.6 mm×250 mm, 4 μm) by gradient elution with a mobile phase of 0.1% aqueous phosphoric acid-acetonitrile at a flow rate of 0.7 mL·min~(-1), detection wavelength of 270 nm, column temperature of 25 ℃, and an injection volume of 5 μL. The fingerprint similarity of 20 batches of Bidentis Herba ranged from 0.775 to 0.979. A total of 20 common peaks were identified, and seven components were confirmed through comparison with reference substances: neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, isochlorogenic acid C, rutin, and hyperoside. These seven components exhibited good linearity within the ranges of 3.4-67.4, 33.0-660.3, 26.6-531.2, 3.5-70.5, 6.2-124.9, 2.4-48.3, and 4.6-91.5 μg·mL~(-1), respectively, with correlation coefficients(r) greater than 0.999. The average recovery rates ranged from 96.47% to 104.6%. CA and PCA classified the 20 batches of Bidentis Herba into two categories. PCA yielded two principal components, with a cumulative variance contribution rate of 80.557%. The established HPLC fingerprints and multi-component content determination method are simple and accurate, providing a scientific basis for the quality control and quality standard formulation of Bidentis Herba.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Chemometrics/methods* ; Bidens/chemistry* ; Principal Component Analysis

This study established the HPLC fingerprints, characteristic chromatograms, and a multi-component content determination method for Bidens bipinnata and B. biternata. The chemical pattern recognition analysis was then employed to clarify the characteristic indexes of quality differences between the two original plants of Bidentis Herba, providing a reference for establishing the quality standards of Bidentis Herba. HPLC was launched on an Agilent Poroshell 120 EC-C_(18) chromatographic column(4.6 mm×250 mm, 4 μm) by gradient elution with a mobile phase of 0.1% aqueous phosphoric acid-acetonitrile at a flow rate of 0.7 mL·min~(-1), detection wavelength of 270 nm, column temperature of 25 ℃, and an injection volume of 5 μL. The similarity between the fingerprints of 18 batches of Bidentis Herba samples and the common pattern(R) ranged from 0.572 to 0.933. A total of 23 chromatographic peaks were calibrated. Through comparison with the reference substances, six components(neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, rutin, and hyperoside) were identified and subjected to quantitative analysis. The characteristic fingerprints of B. bipinnata and B. biternata were calibrated with 20 and 17 characteristic peaks, respectively. Among them, peaks 8, 9, 22, and 23 were the characteristic peaks of B. bipinnata, and peak 7 was the characteristic peak of B. biternata, which can be used to distinguish the two original plants of Bidentis Herba. The relative standard deviation of the content of the above-mentioned six components ranged from 36% to 123%. The cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) classified the 18 batches of Bidentis Herba samples into two categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, three characteristic indexes, rutin, isochlorogenic acid A, and isochlorogenic acid B, were identified. The analytical method established in this study can comprehensively evaluate the consistency of Bidentis Herba samples derived from different original plants, specifically identify the differential components between them, and effectively distinguish the two original plants of Bidentis Herba, providing a basis for the differentiation between different original plants and the quality control of Bidentis Herba.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Bidens/chemistry*

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with IgD multiple myeloma (MM). METHODS: The clinical data of 8 patients with IgD MM admitted to Gansu Provincial Hospital from September 2013 to February 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: Among the 8 enrolled patients, there were 4 males and 4 females, with a median age of 60 (44-74) years. All patients had symptoms of renal insufficiency and anemia. There were 3 cases of bone invasion, 3 cases of splenomegaly, 7 cases of IgD-λ type, and 1 case of IgD-κ type. FISH examination was performed in 7 cases, and 6 of them were positive for 1q21 . There were 6 cases in DS stage III and 2 cases in DS stage II; According to ISS staging, there were 6 cases in stage III, 1 case in stage II, and 1 case in stage I; According to R-ISS staging, there were 5 cases in stage III and 3 cases in stage II. All patients received bortezomib-based combination chemotherapy, with 1 case undergoing autologous stem cell transplantation (ASCT) and 2 cases receiving daratumumab in combination. The median treatment period was 6 (1-15) cycles. The short-term efficacy was evaluated after 4-6 courses of treatment. Among the 6 patients with assessable efficacy, 1 case experienced disease progression (PD), and 5 cases achieved complete remission (CR). The median follow-up time was 26 (11-33) months, and the median progression-free survival (PFS) and median overall survival (OS) of the patients were 11.25 (3-26) months and 18.5 (4-33) months, respectively. Among the 8 patients, 4 cases died. Among the deceased patients, 3 cases were in R-ISS stage III and 3 cases were 1q21 positive. 2 of the 5 patients with early CR died due to disease progression. CONCLUSION The incidence of IgD MM is low, the symptoms of early renal damage, blood system damage and bone erosion in IgD MM patients are obvious, and the median survival time is short. ASCT and / or daratumumab may bring lasting relief for IgD MM patients, but large-scale clinical studies are still needed.
Humans ; Multiple Myeloma/therapy* ; Middle Aged ; Male ; Female ; Aged ; Prognosis ; Immunoglobulin D ; Adult ; Retrospective Studies

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with T-cell large granular lymphocytic leukemia (T-LGLL). METHODS: The clinical data of 7 patients with T-LGLL in Gansu Provincial Hospital from March 2016 to June 2023 were analyzed retrospectively. RESULTS: Among the 7 patients, 5 were male and 2 were female, with a median age of 51(28-83) years old. At the onset of illness, 6 cases showed symptoms of fatigue and anemia, 4 cases had enlarged lymph nodes, and 5 cases had splenomegaly. Examination showed that 4 cases were antinuclear antibody(ANA) positive, 5 cases were anemia. The median hemoglobin (Hb) level was 83(61-151) g/L, the median white blood cell count (WBC) was 5.6(2.0-8.7)×10⁹ /L, and the median percentage of lymphocytes in peripheral blood was 66.2(13.9-89.1)%. There were 3 cases with extremely active bone marrow hyperplasia, 2 cases with active hyperplasia, and 2 cases with decreased hyperplasia. There were 5 cases with mild myelofibrosis (MF-1), and 1 case with moderate myelofibrosis (MF-2). The median percentage of T cells was 64.3 (31.5-80.6)%. 5 cases showed the classic immunophenotype (CD3 ⁺ CD4^- CD8 ⁺), 6 cases were CD57 ⁺, 3 cases were TCRα/β ⁺, and 3 cases were TCRγ/δ ⁺. TCRG rearrangement was detected in 5 cases.The median follow-up time was 55(4-87) months, one patient died of heart disease, and the other 6 patients are surviving. CONCLUSION The incidence of T-LGLL is low. The initial symptoms of T-LGLL include anemia, fatigue, lymph node enlargement, splenomegaly, and higher percentage of lymphocytes in peripheral blood, the percentage of abnormal T cells in bone marrow was significantly increased. Analysis of flow cytometric immunophenotyping, TCR gene rearrangement, and hot spot genes such as STAT3 and STAT5b, can improve the diagnostic accuracy.
Humans ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Male ; Middle Aged ; Female ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; Retrospective Studies

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.