Objective To study the relationship between environmental chemical elements,vires infection and dilated cardiomyopathy(DCM).Methods In 2008,233 patients with DCM(case group)and 150 patient with stable angina(control group)were chosen in Liaocheng People's Hospital and Yanggu People's Hospital,Shandong province.Population distribution and disease history were surveyed in the two groups.Human myocardial antibody IgG(AMA-IgG),Coxsackie B virus IgG(CBV-IgG),Adenofirus antibody IgG(ADV-IgG)were detected by ELISA in both the case group and the control group.Serum trace elements were detected in the two groups.The general chemical and toxicological indicators in drinking water of the high-and the low-incidence aireas of the disease were control group[60.00%(90/150),χ2=13.80,P<0.01)].Per capita annual income(Yuan,RMB)in the case group (3207.82±618.51)was lower than that of the control group[(5086.61±886.12),t=24.40,P<0.01].Personal alcohol consumption in the case group[(175.00±160.50)g/d]was higher than that of the control group[(110.22±100.03)g/d,t=4.40,P<0.01)].The rate of myocarditis in the case group[5.15%(12/233)]was higher than ADV-IgG in the cage group were 7.78%(7/90),6.67%(6/90)and 6.67%(6/90),respectively.Compared with those in the control group[3.33%(2/60),5.00%(3/60)and 5.00%(3/60),χ2=1.26,0.18,0.18,all P>0.05],no mg/L]in drinking water of the high-incidence areas were significantly higher than that of iron[(0.39±0.67)mg/L,t=2.11,P<0.05]and that of manganese[(0.15±0.14)mg/L,t=3.01,P<0.01]in the low-incidence arefas.The content of semm iron[(69.1±57.8)μmol/L]in the case group evidently exceeded the normal range(15.6-35.9 μmol/L)and obviously higher than that in the control group[(20.0±17.5)μmol/L,t=5.04,P<0.01].Conclusions Theso data do not support that DCM is related with persistent virus infection and autoimmunization.DCM is probably related with low incomes,high alcohol consumption,myocarditis,high iron and manganese contents in drinking water and high content of serum iron.

Objective:To investigate the effect and safety of rituximab, programmed death 1 (PD-1) monoclonal antibody, and Bruton tyrosine kinase (BTK) inhibitor on elderly refractory primary central nervous system lymphoma (PCNSL).Methods:The clinical data of an elderly patient with refractory PCNSL treated with the combination of rituximab, PD-1 monoclonal antibody and BTK inhibitor in the First Hospital of Jilin University in February 2020 were retrospectively analyzed. The relevant literature was reviewed.Results:The patient had primary central nervous system diffuse large B-cell lymphoma (high-risk group), and the Memorial Sloan Kettering Cancer Center (MSKCC) score was 2 (estimated overall survival time was 7 months). Disease progressed after 1 course of treatment. Complete remission was achieved after the therapy of rituximab, PD-1 monoclonal antibody combined with BTK inhibitor. PD-1 monoclonal antibody maintenance therapy was performed and patient was followed up until November 17, 2021. The patient's condition was stable. The second progression-free survival (PFS) time was 20 months, and the overall survival time was 21 months. The patient well tolerated the new drug treatment, and no adverse reactions of grade 3 or above occurred.Conclusions:The new targeted combination therapy can be used as a treatment option for elderly PCNSL patients, which can further improve the curative effect and significantly improve the prognosis.

AIM To investigate the effects of stir-frying,processing with butter and carbonizing by stir-frying on oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis.METHODS The volatile oils and fatty oils were extracted by steam distillation method and Soxhlet extraction method,respectively,after which the extraction rates were determined.GC-MS was applied to analyzing the kinds and relative contents of oil components,after which cluster analysis was performed.RESULTS After the processing,the two medicinal materials demonstrated increased extraction rates of fatty oils and decreased extraction rates of volatile oils(except for processing with butter),the extraction rates of oil components in Gleditsiae sinensis Fructus were higher than those in Gleditsiae Fructus Abnormalis,and the reduced relative contents of toxic olefin benzene components were observable.CONCLUSION The kinds and relative contents of oil components in Gleditsiae sinensis Fructus and Gleditsiae Fructus Abnormalis exist obvious differences,the former displays better medicinal quality,whose processing mechanism in alleviating dryness and strength may contribute to the reduction of relative contents of toxic olefin benzene components.

Aim To explore the mechanism of Yanghe decoction-containing serum on the migration and inva-sion of MCF-7 breast cancer cells in a co-culture sys-tem with M2 tumor-associated macrophages(TAMs)based on the paracrine epidermal growth factor(EGF)/epidermal growth factor receptor(EGFR)sig-naling pathway.Methods The M2-type TAMs model was induced from THP-1 monocytic cell line through in vitro treatment with phorbol 12-myristate 13-acetate(PMA)and recombinant human macrophage colony-stimulating factor(M-CSF).The MCF-7 cells were co-cultured with M2-type TAMs using a Transwell non-contact co-culture system to evaluate their effects on migration and invasion.Subsequently,the cells were intervened with serum containing Yanghe decoction,and the proliferation of MCF-7 cells was detected using the CCK-8 assay,while their lateral migration ability was assessed through scratch assays.The invasion and vertical migration abilities of the cells were evaluated separately using Transwell assays,and the concentra-tion of EGF was measured using ELISA.Finally,the expression of EGFR,MCP-1,and MMP9 proteins was detected using Western blot.Results Compared to the control group,Yanghe decoction-containing serum in-hibited the proliferation of MCF-7 cells before and after co-culture.The serum reduced the scratch healing a-bility before and after co-culture and decreased their migration and invasion abilities.Additionally,Yanghe decoction-containing serum reduced the levels of EGF before and after co-culture and decreased the expres-sion of EGFR,MCP-1,and MMP9 proteins before and after+co-culture.Conclusion Yanghe decoction-containing serum can inhibit the migration and invasion of breast cancer MCF-7 cells before and after co-cul-ture with M2 TAMs.This effect may be related to the inhibition of the EGF-EGFR signaling pathway.

BACKGROUNDAvailable drug-eluting stents (DES) have achieved great success in reducing restenosis rates. Recently, investigators have demonstrated that the durable polymer carrier plays a significant role in DES-related hypersensitive reaction and delays vessel healing. TIVOLI stent is a novel sirolimus-eluting coronary stent with biodegradable coating containing sirolimus and polylactic-co-glycolic acid (PLGA) polymer. The present study sought to evaluate the effectiveness and safety of the TIVOLI biodegradable-polymer-based sirolimus-eluting stent in treating patients with coronary artery disease.

METHODSA prospective, multicenter clinical trial comparing TIVOLI biodegradable coated sirolimus-eluting stent with ENDEAVOR zotarolimus-eluting stent was conducted in 324 patients (TIVOLI group: 168 patients; ENDEAVOR group: 156 patients) at 12 centers in China to demonstrate the non-inferiority of in-stent late loss with TIVOLI stent compared to ENDEAVOR stent in subjects with a maximum of two de novo native coronary artery lesions (lesion length &le; 40 mm, reference vessel diameter 2.25-4.00 mm). The primary end point was angiographic in-stent late loss at 8-month. The secondary end points were clinical outcomes at 2 years, including major adverse cardiac events (cardiac death, myocardial infarction, or target-lesion revascularization) and stent thrombosis.

RESULTSAngiographic late lumen loss at 8 months in the TIVOLI group was superior to the ENDEAVOR group (in-stent (0.25 ± 0.33) mm vs. (0.57 ± 0.55) mm, diff (95%CI) -0.23 (-0.32, -0.14), P < 0.0001; in-segment (0.25 ± 0.33) mm vs. (0.42 ± 0.55) mm, diff (95%CI) -0.13 (-0.23, -0.02), P = 0.0083). The rate of in-stent binary restenosis at 8 months was reduced from 8.6% in the ENDEAVOR group to 2.9% in the TIVOLI group (P = 0.0229). Compared to ENDEAVOR stent, TIVOLI stent resulted in a significant reduction in target-lesion revascularization (4.2% vs. 9.6%, P = 0.0495) at 2 years. The two-year major adverse cardiac events (MACE) rate was lower for the TIVOLI group, but not significantly different (6.6% vs. 10.9%, P = 0.1630).

CONCLUSIONSTIVOLI was superior to ENDEAVOR stent with respect to late lumen loss at 8 months, and it yielded both lower rates of angiographic binary restenosis at 8 months and target lesion revascularization (TLR) at 2 years. The MACE rate at 2 years was comparable in both groups.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Coronary Artery Disease ; drug therapy ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Polymers ; chemistry ; Sirolimus ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Objective:To evaluate the clinical relevant effect of hospital-wide blood glucose management in perioperative cholelithiasis patients with type 2 diabetes.Methods:The subjects of the study were patients with type 2 diabetes mellitus complicated with cholelithiasis who were treated at the Baiqiu'en Hospital in Shanxi from September 2022 to October 2023. The patients were divided into hospital-wide blood sugar management group and conventional treatment group, according to different blood glucose management they received. The differences in preoperative blood glucose control, length of stay, postoperative complications, and hospitalization expenses between the two groups were compared.Results:Compare based on the median (quartiles) of the observed indicators, patients with cholelithiasis who underwent hospital-wide blood glucose management based on insulin pumps had a higher proportion of time in range [72.00(70.21, 82.90)% vs. 64.80 (61.55,70.50)%, P<0.001)], lower average blood glucose level [9.00 (8.55, 10.44) mmol/L vs. 11.50 (10.50, 12.50) mmol/L, P<0.001], and shorter hospital stay [8.00 (7.00,13.00) days vs. 10.00 (8.00, 12.00) ) days, P<0.05]. Moreover, the incidence of postoperative complications was lower [5(11.11)% vs. 15(33.33)%, P<0.05], and hospitalization expenses were lower [16 535.34 (14 271.44, 29 569.23) yuan vs. 18 633.85 (17 482.66) yuan , 22 855.02) yuan, P<0.05] in patients who received hospital-wide blood glucose management. Conclusion:Hospital-wide blood glucose management based on insulin pumps showed favorable effects in the perioperative clinical application in cholelithiasis patients with type 2 diabetes, and could contribute to shortening the average length of stay, reducing hospitalization costs, and reducing postoperative complications.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.

Objective:To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia(AML).Methods:High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center,the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML.The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML.The expression of IGF2BP3 in two anthracycline-resistant cell lines(HL60/ADR,K562/ADR)was detected by RT-qPCR and Western blot,and the expression difference of IGF2BP3 was compared with that in sensitive cells(HL60,K562).The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML,and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis.Results:In the bone marrow primary leukemia cells of 27 AML patients in our center,the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients(P=0.0343).The expression of IGF2BP3 in leukemia patients with extramedullary infiltration(EMI)was significantly higher than that in AML patients without extramedullary infiltration(P=0.0049).Compared with healthy subjects(n=20),IGF2BP3 expression in AML patients(n=26)was higher(P=0.0009).The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines(HL60/ADR,K562/ADR)was significantly higher than that in the sensitive cell lines(K562/ADR vs K562,P=0.0430;HL60/ADR vs HL60,P=0.7369).Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells(P＜0.001).qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive(P=0.002).High expression of IGF2BP3 was associated with poor prognosis in AML(P＜0.05)in 3 large sample cohorts of AML patients.Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival(EFS,HR=1.887,P=0.024)and overall survival(OS,HR=1.619,P=0.016).Conclusion:The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML,suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.

OBJECTIVETo analyze the correlation between pituitary stalk interruption syndrome (PSIS) and prokineticin receptor 2 (PROKR2) and prokineticin 2 (RROK2) mutations.

METHODSPROKR2 and RROK2 genotypes were identified by multiplex polymerase chain reaction analysis with exon-flanking primers and by automated sequencing techniques with peripheral blood DNA samples from 59 patients with PSIS.

RESULTSOf these 59 PSIS patients, 6 showed intragenic deletions at the PROKR2 locus. Of them, 5 patients exhibited intragenic subsititution of exon 2 (c.991G>A), and the remaining one patient exhibited intragenic subsititution of exon 2 (c.1057C>T). No PROK2 mutation was found in these PSIS patients.

CONCLUSIONPROKR2 may be the susceptibility gene of PSIS.

Exons ; Gastrointestinal Hormones ; Genotype ; Humans ; Mutation ; Neuropeptides ; Pituitary Diseases ; Receptors, G-Protein-Coupled ; Receptors, Peptide

The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of five major active constituents in the traditional Chinese medicinal preparation Xingxiong injection (XXI) in rat plasma, including quercetin 3-O-rutinoside (QCR), kaempferol 3-O-rutinoside (KFR), isorhamnetin 3-O-rutinoside (ISR), bilobalide (BB), and ligustrazine (LGT). The plasma samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was achieved on a Waters Symmetry C analytical column (2.1 mm × 100 mm, 3.5 μm) with a mobile phase of 0.1% aqueous formic acid (A)-acetonitrile (B). Quantitation of the five bioactive constituents was achieved. Naringin was used as the internal standard (IS). All the calibration curves showed good linearity (r > 0.996) over the concentration range, with the lowest limit of quantification (LLOQ) between 2-18 ng·mL. The intra- and inter-day accuracy and precision of the analytes were both within acceptable limits. Moreover, satisfactory extraction recoveries (90.92%-104.03%) were obtained by protein precipitation. The validated method was successfully applied to a pharmacokinetic study of XXI in rats after intravenous administration at three doses. The pharmacokinetic parameters of the five compounds varied in a dose-dependent manner within the tested dosage range. The present study was the first report of pharmacokinetic study for XXI.
Animals ; Bilobalides ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Disaccharides ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Flavonoids ; blood ; pharmacokinetics ; Glucosides ; blood ; pharmacokinetics ; Kaempferols ; blood ; pharmacokinetics ; Pyrazines ; blood ; pharmacokinetics ; Quercetin ; analogs & derivatives ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods