OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVE: To explore the clinical characteristics and prognosis of children with SIL-TAL1-positive T-cell acute lymphoblastic leukemia ( SIL-TAL1⁺ T-ALL). METHODS: The clinical data of 110 children with newly diagnosed T-ALL admitted to the pediatric department of our hospital from January 2010 to December 2018 were reviewed to compare the clinical characteristics, treatment response and prognosis between SIL-TAL1⁺ group and SIL-TAL1^-group. RESULTS: Among the 110 children with T-ALL, 25 cases (22.7%) were in the SIL-TAL1⁺ group and 85 cases (77.3%) in the SIL-TAL1^- group. The white blood cell (WBC) count in the SIL-TAL1⁺ group was significantly higher than that in the SIL-TAL1^- group (P < 0.05), while the other clinical characteristics and treatment response were not significantly different between the two groups. The 5-year overall survival (OS) rates of SIL-TAL1⁺ group and SIL-TAL1^- group were 80.0% and 75.5%, and 5-year disease-free survival (DFS) rates were 76.0% and 72.9%, respectively. There were no significant differences in OS rate and DFS rate between the two groups ( P >0.05). In children aged < 10 years, the 5-year OS rate of SIL-TAL1⁺ group and SIL-TAL1^- group was 100% and 75.1%, respectively, and the difference between the two groups was statistically significant (P < 0.05). CONCLUSION Although the WBC level is significantly higher in children with SIL-TAL1⁺ T-ALL than that in those with SIL-TAL1^- T-ALL, the treatment efficacy is similar between the two groups. In children aged < 10 years, the longterm survival rate is superior in the SIL-TAL1⁺ group.
Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis* ; Prognosis ; Child ; Male ; Female ; Survival Rate ; T-Cell Acute Lymphocytic Leukemia Protein 1 ; Child, Preschool ; Oncogene Proteins, Fusion ; Leukocyte Count

Objective:To determine the differential expressions of long non-coding RNA(lncRNA)and messenger RNA(mRNA)in normal and asthenospermia(AS)men and analyze their biological significance in AS.Methods:We isolated and ex-tracted total RNAs from 9 normal and 9 AS sperm samples,determined the expressions of RNAs in the sperm using the DNBSEQ se-quencing platform,and analyzed their relevant functions by gene ontology enrichment(GO)and Kyoto encyclopedia of genes and ge-nomes pathway(KEGG)analyses.Results:An average of 10.64G data was generated per group,with 282 185 RNAs detected,in-cluding 107 009 lncRNAs.Among the total number of lncRNAs,15 157 were differentially expressed,2 190 upregulated and 12 967 downregulated;and among the 19 514 mRNAs,13 736 were differentially expressed,4 995 upregulated and 8 741 downregulated.Differentially expressed genes were enriched mainly in the sperm cell membrane and the pathways related to the ion channel functions,sperm development and fertilization.Conclusion:Differentially expressed lncRNAs and mRNAs can be identified by sequencing a-nalysis of AS and normal sperm.Regulation of sperm function through membrane ion channels may contribute to the development of AS,which provides a molecular basis for further research on AS.

AIM To analyze the metabolites of nobiletin in rats in vivo based on characteristic ions.METHODS Ten rats were assigned into administration group and control group,and given intragastric administration of the 0.5％CMC-Na suspension of nobiletin(250 mg/kg)and 0.5％CMC-Na solution,respectively,after which plasma,urine and feces were collected,solid phase extraction method was adopted in pretreatment,UHPLC-HRMS analysis was performed.The candidate metabolites were systematically described according to diagnostic product ions,chromatographic retention time,accurate molecular weight and neutral loss fragments,after which accurate metabolites were obtained in the established metabolite data set with-CH3(m/z 15)characteristic ions as a baits.RESULTS A total of 64 metabolites were identified,whose main metabolic pathways were glucuronidation,sulfation,hydrogenation and their compound reactions.CONCLUSION This experiment elucidates the metabolites of nobiletin in rats in vivo,which provides a new reference for its further development.

AIM To study the chemical constituents from the ethyl acetate fraction of Baccharis trimera(Less.)DC.METHODS The ethyl acetate fraction of B.trimera was isolated and purified by macroporous resin D101,Sephadex LH-20 gel,silica gel and other chromatographic techniques,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-three compounds were isolated and identified as 15,16-epoxy-15α-methoxy-ent-clerod-3-en-18-oic acid(1),13-epi-15,16-epoxy-15α-methoxy-ent-clerod-3-en-18-oic acid(2),methyltrineracetal(3),epimethyltrineracetal(4),trinerolide(5),15-epitrinerolide(6),18-methylmalonyl-7α-hydroxy-meth-yltrineracetal(7),18-methylmalonyl-7α-hydroxy-epimethyltriner-acetal(8),18-methylmalonyl-methyltrineracetal(9),18-methylmalonyl-epi-methyltrineracetal(10),methy 3,5-dicaffeoylquinate(11),8-dimetho-xyflavone(12),4',7-dihydroxy-5-methoxyflavanone(13),4-(3',4'-dihydroxycinna-moyl)-oxy-methy-lcinnamate(14),3',7-dihydroxy-4',6,8-trimethoxy-flavone(15),erigeroflavanone(16),nepetin(17),4,2',4',β-tetrahydroxy-6'-methoxy-α,β-dihydrochalcone(18),eugeniyl-O-β-D-glucoside(19),7-hydroxyl-5,6,3',4'-tetramethoxylflavone(20),phomoxanthone J(21),18-acetyl-7α-hydroxy-methyltrineracetal(22),18-acetyl-7α-hydroxy-epimethyltrineracetal(23).CONCLUSION Compounds 3-10 and 22-23 are epimers isolated from this plant for the first time.Compounds 11-16,18-21 are first isolated from genus Baccharis.

Objective:To investigate the effects of regular yoga practice on pulmonary function and mechanical parameters of diaphragm.Methods:Eighty regular yoga practitioners, including 40 practicing for≤5 year (yoga≤5 years group) and 40 for>5 year (yoga>5 years group) were recruited in Shanxi Norman Bethune Hospital from January 2024 to April 2024; and 40 sedentary subjects were also recruited as the control group. The diaphragmatic motion was evaluated by two-dimensional ultrasound and speckle tracking ultrasound in all subjects, the parameters, including displacement, fractional thickening, strain and strain rate of diaphragm were observed at rest and deep breathing. At the same time, the pulmonary function tests were performed, the indexes including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV 1) and one-second rate (FEV 1/FVC) were measured in all subjects. The mechanical parameters of diaphragm and the pulmonary function were compared among three groups. Results:There were no significant differences in gender ( χ2= 0.346), age ( F=1.16), height ( F=0.45), weight ( F=0.11) and body mass index (BMI) ( F=0.07) among the three groups (all P>0.05).At the rest status, there was no significant difference in diaphragm displacement, thickening rate and strain among three groups ( F=1.21, 2.10 and 0.23,all P>0.05); the strain rate of yoga>5 years group was lower than that of other two groups ( t=-4.23、-4.10, all P<0.05); however, there was no significant difference between yoga≤5 years group and control group ( t=-0.06, P>0.05). During deep breathing, the increment of displacement, thickening rate, strain and strain rate of diaphragm in yoga>5 years group was larger than that in other tow groups, while the increment of yoga≤5 years group was larger than that in control group ( F=25.82, 60.99, 17.29 and 52.46, all P<0.05); the increment of FVC, FEV 1 and FEV 1/FVC in yoga>5 years group was larger than other two groups, whilc the increment of yoga≤5 years group was larger than that of sedentary group (F=4.49, 7.32 and 39.71, all P<0.05). The diaphragmatic displacement was positively correlated with FVC ( r=0.290, P<0.05), and diaphragmatic displacement and thickening rate were positively correlated with FEV 1 and FEV 1/FVC (0.333 and 0.448, 0.231 and 0.599, all P<0.05), the strain and strain rate of diaphragm were negatively correlated with FEV 1 and FEV 1/FVC ( r=-0.399 and -0.719, -0.355 and -0.796, all P<0.05). Conclusion:The regular yoga practice can improve the movement capacity and efficiency of diaphragm, improve the pulmonary function, and there is a negative correlation between the strain rate and the mechanical parameters of diaphragm and FEV 1, FEV 1/FVC.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Objective:To explore the expressions and clinical significances of tripartite motif-containing protein 28 (TRIM28), 3-phosphoinositide-dependent protein kinase-1 (PDK1), and N-cadherin in pancreatic carcinoma.Methods:A total of 72 patients diagnosed with pancreatic carcinoma underwent radical resection in the Department of Hepatobiliary Surgery, Binzhou People′s Hospital from January 2009 to November 2022 were selected, all of which were pathologically diagnosed as pancreatic ductal adenocarcinoma (PDAC). Immunohistochemistry was used to detect the expression of TRIM28, PDK1, and N-cadherin in 72 cases of pancreatic carcinoma and paracancerous tissues, to explore the correlation between the expression of them and the clinicopathological features of pancreatic carcinoma, and to analyze the influence of their expression and clinicopathological characteristics on the prognosis of patients. The count data were expressed as the number of cases and percentage, and the Chi-square test was used for comparison between groups. Spearman method was used for correlation analysis. Kaplan-Meier method was used for survival analysis, and Log-rank test was used to compare the survival rate, and univariate and multivariate Cox regression analysis were used to analyze the risk factors affecting prognosis.Results:The positive rates of TRIM28 (72.22%), PDK1 (65.28%) and N-cadherin (61.11%) in PDAC were significantly higher than those in para-cancerous tissues (26.39%, 33.33%, 34.72%). Moreover, the patients with high expression of the three had the characteristics of low differentiation, late stage, and lymph node metastasis ( P<0.05). TRIM28 was positively correlated with PDK1 and N-cadherin expression in PDAC ( r=0.720, P<0.001; r=0.714, P<0.001), N-cadherin and PDK1 expression in PDAC was also positively correlated ( r=0.854, P<0.001). Kaplan-Meier survival curve showed that the 2-year survival rate of patients with positive TRIM28, PDK1 and N-cadherin (13.46%, 14.89%, 13.64%) was significantly lower than that of patients with negative tumor (50.00%, 40.00%, 39.29%), the differences were statistically significant ( P<0.05). Univariate Cox regression analysis showed that patients with poor differentiation, nerve infiltration and lymph node metastasis, TNM stage Ⅲ+ Ⅳ, TRIM28 positive, PDK1 positive and N-cadherin positive had a significantly increased risk of death within 2 years after surgery ( P<0.05). Multivariate Cox regression analysis showed that poor differentiation, nerve infiltration, TNM stage Ⅲ+ Ⅳ and TRIM28 positive were independent risk factors for poor prognosis of patients with PDAC ( P<0.05). Conclusions:TRIM28, PDK1 and N-cadherin are highly expressed in PDAC, and the expression level is significantly correlated with the malignant degree of PDAC. TRIM28 is an independent risk factor for the prognosis of patients with PDAC.

Objective:To investigate the clinical efficacy and safety of ixazomib-containing regimens in the treatment of patients with multiple myeloma(MM).Methods:A retrospective analysis was performed on the clinical efficacy and adverse reactions of 32 MM patients treated with a combined regimen containing ixazomib in the Hematology Department of the First People's Hospital of Lianyungang from January 2020 to February 2022.Among the 32 patients,15 patients were relapsed and refractory multiple myeloma(R/RMM)(R/RMM group),17 patients who responded to bortezomib induction therapy but converted to ixazomib-containing regimen due to adverse events(AE)or other reasons(conversion treatment group).The treatment included IPD regimen(ixazomib+pomalidomide+dexamethasone),IRD regimen(ixazomib+lenalidomide+dexamethasone),ICD regimen(ixazomib+cyclophosphamide+dexamethasone),ID regimen(ixazomib+dexamethasone).Results:Of 15 R/RMM patients,overall response rate(ORR)was 53.3％(8/15),among them,1 achieved complete response(CR),2 achieved very good partial response(VGPR)and 5 achieved partial response(PR).The ORR of the IPD,IRD,ICD and ID regimen group were 100％(3/3),42.9％(3/7),33.3％(1/3),50％(1/2),respectively,there was no statistically significant difference in ORR between four groups(x2=3.375,P=0.452).The ORR of patients was 50％after first-line therapy,42.9％after second line therapy,60％after third line therapy or more,with no statistically significant difference among them(x2=2.164,P=0.730).In conversion treatment group,ORR was 88.2％(15/17),among them,6 patients achieved CR,5 patients achieved VGPR and 4 patients achieved PR.There was no statistically significant difference in ORR between the IPD(100％,3/3),IRD(100％,6/6),ICD(100％,3/3)and ID(60％,3/5)regimen groups(x2=3.737,P=0.184).The median progression-free survival(PFS)time of R/RMM patients was 9 months(95％CI:6.6-11.4 months),the median overall survival(OS)time was 18 months(95％CI:11.8-24.4 months).The median PFS time of conversion treatment group was 15 months(95％CI:7.3-22.7 months),the median OS time not reached.A total of 10 patients suffered grade 3-4 adverse event(AE).The common hematological toxicities were leukocytopenia,anemia,thrombocytopenia.The common non-hematological toxicities were gastrointestinal symptoms(diarrhea,nausea and vomit),peripheral neuropathy,fatigue and infections.Grade 1-2 peripheral neurotoxicity occurred in 7 patients.Conclusion:The ixazomib-based chemotherapy regimens are safe and effective in R/RMM therapy,particularly for conversion patients who are effective for bortezomib therapy.The AE was manageable and safe.