Objective We aimed to observe the effect of the traditional Chinese medicine(TCM)-based"tertiary hospital-community integrated"treatment program in patients with diabetic kidney disease.Methods A total of 126 patients from the Jiangtai and Cuigezhuang Communities in Chaoyang District were randomly divided into the experimental group and the control group(n=63 patients per group).In the experimental group,the"tertiary hospital-community integrated"treatment program was implemented(including TCM differentiated health preservation,chronic disease management,comprehensive diagnosis and treatment program of integrated Chinese and Western medicine),while in the control group,the existing chronic disease diagnosis,treatment,and management program in the community was implemented(including chronic disease management with regular follow-ups,diagnosis and treatment program of Western medicine).The observation period was 6 months,with 3 months as a course of treatment.The 24 h urine total protein level(24 hUTP),the serum level of creatinine(Scr),and the estimated glomerular filtration rate(eGFR)were compared between the two groups,as well as the effective rates of 24 hUTP,Scr,and eGFR,the rate of achieving standard glucose levels and normal lipid metabolism,including low-density lipoprotein-cholesterol(LDL-C),triglyceride(TG),and glycosylated hemoglobin(GHB),the level of patients'self-management,and the medical service in utilization.Results There were 120 patients included for analysis(60 in the experimental group and 60 in the control group).The difference in 24 hUTP was significantly different(P＜0.05),while Scr and eGFR were not statistically different between the experimental and control groups after 3 months of treatment.The differences in 24 hUTP,Scr,and eGFR were statistically significant after 6 months(P＜0.05).After 6 months of treatment in both groups,the effective rates of 24 hUTP,Scr,and eGFR were higher in the experimental group than in the control group(78.3％,48.3％,and 50.0％in the experimental group and 35.0％,18.3％,and 15.0％in the control group,respectively)(P＜0.05);after 6 months,the LDL-C,TG,and GHB qualified rates were higher in the experimental group than in the control group(75.0％,83.3％,and 71.7％in the experimental group and 56.7％,63.3％,and 46.7％in the control group,respectively;P＜0.05);comparing the self-management levels of the two groups after 3 and 6 months of treatment,the total self-management score and the total self-efficacy score were both higher in the experimental group than in the control group(P＜0.05);comparing the time of hospitalization and hospitalization costs of the two groups 6 months after enrollment,the time of hospitalization and hospitalization costs were lower in the experimental group(P＜0.05).Conclusion The"tertiary hospital-community integrated"TCM-based treatment program improves renal function,glucose and lipid metabolism,and patients'self-management;it can reduce the economic burden of families,save medical resources,and improve the utilization of medical services.

Objective:To investigate the diagnostic efficacy of targeted biopsy combined with regional systematic biopsy in prostate cancer(PCa)in patients with prostate imaging reporting and data system v2.1(PI-RADS v2.1)4-5.Methods:From January 2023 to October 2023,patients who underwent prostate biopsy for the first time with total prostate specific antigen(tPSA)≤20 ng/mL and had a multi-parametric magnetic resonance imaging(mpMRI)PI-RADS of 4-5 in Peking University First Hospital were prospectively collected.All the patients underwent transrectal ultrasound-guided cognitive fusion tar-geted biopsy(3 cores)followed by systematic biopsy(12 cores).Various hypothetical biopsy schemes were defined based on different biopsy sites.The detection effectiveness of targeted biopsy combined with regional systematic biopsy and other biopsy schemes for prostate cancer were compared using Cochran's Q and McNemar tests.Results:A total of 255 patients were enrolled,of whom 204(80.0％)were de-tected with prostate adenocarcinoma and 187(73.3％)were clinically significant with prostate cancer(csPCa).The detection rate of PCa with targeted biopsy was significantly lower than that of targeted biopsy combined with 12-core system biopsy(77.3％vs.80.0％,P=0.016),and 71.4％(5/7)of the missed patients was csPCa.There was no significant difference in the detection rate between targeted biopsy combined with 4-core regional system biopsy and 12-core system biopsy(P＞0.999),and 1 case of csPCa and clinically insignificant prostate cancer(cisPCa)were missed.There was no significant difference in the detection rate of PCa between targeted combined regional system biopsy and targeted combined lateral or traditional 6-core system biopsy and the number of cores were reduced.Missed diag-nosis of targeted biopsy was correlated with the maximum diameter of the lesion(OR=0.086,95％CI:0.013-0.562,P=0.010).For the patients with PI-RADS 5,only 1 case of PCa was missed in 122 cases by targeted biopsy alone.For patients with PI-RADS 4,6 PCa cases were missed among the 133 patients with targeted biopsy alone,and 1 case of csPCa and cisPCa were missed by targeted biopsy com-bined with regional system biopsy.The statistics of positive core counts for different biopsy schemes indi-cated that targeted combined regional systematic biopsy had a higher proportion of positive cores second only to targeted biopsy alone.Conclusion:Targeted biopsy combined with regional systematic biopsy has high diagnostic efficacy in patients with PI-RADS 4-5 and can be considered as one of the improved schemes for combined biopsy.Targeted biopsy alone is also a feasible option for patients for patients with a PI-RADS score of 5.

Objective To explore the effect of microRNA-22-3p (miR-22-3p) regulating the expression of Kruppel-like factor 6 (KLF6) on the cardiomyocyte-like differentiation of bone marrow mesenchymal stem cell (BMSC). Methods Rat BMSC was isolated and cultured,and the third-generation BMSC was divided into a control group,a 5-azacytidine(5-AZA)group,a mimics-NC group,a miR-22-3p mimics group,a miR-22-3p mimics+pcDNA group,and a miR-22-3p mimics+pcDNA-KLF6 group.Real-time fluorescent quantitative PCR (qRT-PCR) was carried out to determine the expression of miR-22-3p and KLF6 in cells.Immunofluorescence staining was employed to detect the expression of Desmin,cardiac troponin T (cTnT),and connexin 43 (Cx43).Western blotting was employed to determine the protein levels of cTnT,Cx43,Desmin,and KLF6,and flow cytometry to detect the apoptosis of BMSC.The targeting relationship between miR-22-3p and KLF6 was analyzed by dual luciferase reporter gene assay. Results Compared with the control group,5-AZA up-regulated the expression of miR-22-3p (q=7.971,P<0.001),Desmin (q=7.876,P<0.001),cTnT (q=10.272,P<0.001),and Cx43 (q=6.256,P<0.001),increased the apoptosis rate of BMSC (q=12.708,P<0.001),and down-regulated the mRNA (q=20.850,P<0.001) and protein (q=11.080,P<0.001) levels of KLF6.Compared with the 5-AZA group and the mimics-NC group,miR-22-3p mimics up-regulated the expression of miR-22-3p (q=3.591,P<0.001;q=11.650,P<0.001),Desmin (q=5.975,P<0.001;q=13.579,P<0.001),cTnT (q=7.133,P<0.001;q=17.548,P<0.001),and Cx43 (q=4.571,P=0.037;q=11.068,P<0.001),and down-regulated the mRNA (q=7.384,P<0.001;q=28.234,P<0.001) and protein (q=4.594,P=0.036;q=15.945,P<0.001) levels of KLF6.The apoptosis rate of miR-22-3p mimics group was lower than that of 5-AZA group (q=8.216,P<0.001).Compared with the miR-22-3p mimics+pcDNA group,miR-22-3p mimics+pcDNA-KLF6 up-regulated the mRNA(q=23.891,P<0.001) and protein(q=13.378,P<0.001)levels of KLF6,down-regulated the expression of Desmin (q=9.505,P<0.001),cTnT (q=10.985,P<0.001),and Cx43 (q=8.301,P<0.001),and increased the apoptosis rate (q=4.713,P=0.029).The dual luciferase reporter gene experiment demonstrated that KLF6 was a potential target gene of miR-22-3p. Conclusion MiR-22-3p promotes cardiomyocyte-like differentiation of BMSC by inhibiting the expression of KLF6.
Animals ; Rats ; Myocytes, Cardiac ; Kruppel-Like Factor 6 ; Connexin 43 ; Desmin ; Cell Differentiation ; Azacitidine/pharmacology* ; Mesenchymal Stem Cells ; RNA, Messenger ; MicroRNAs

OBJECTIVE: To investigate whether ginsenoside Rb1 (Rb1) can protect human umbilical vein endothelial cells (HUVECs) against high glucose-induced apoptosis and examine the underlying mechanism. METHODS: HUVECs were divided into 5 groups: control group (5.5 mmol/L glucose), high glucose (HG, 40 mmol/L) treatment group, Rb1 (50 µ mol/L) treatment group, Rb1 plus HG treatment group, and Rb1 and 3-( RESULTS: Rb1 ameliorated survival in cells in which apoptosis was induced by high glucose (P<0.05 or P<0.01). Upon the addition of Rb1, mitochondrial and intracellular reactive oxygen species generation and malondialdehyde levels were decreased (P<0.01), while the activities of antioxidant enzymes were increased (P<0.05 or P<0.01). Rb1 preserved the mitochondrial membrane potential and reduced the release of Cyt-c from the mitochondria into the cytosol (P<0.01). In addition, Rb1 upregulated mitochondrial biogenesis-associated proteins (P<0.01). Notably, the cytoprotective effects of Rb1 were correlated with SIRT3 signalling pathway activation (P<0.01). The effect of Rb1 against high glucose-induced mitochondria-related apoptosis was restrained by 3-TYP (P<0.05 or P<0.01). CONCLUSION Rb1 could protect HUVECs from high glucose-induced apoptosis by promoting mitochondrial function and suppressing oxidative stress through the SIRT3 signalling pathway.

BackgroundThe pathogenesis of postural tachycardia syndrome (POTS) remains unclear. This study aimed to explore the changes and significance of sulfur dioxide (SO) in patients with POTS.

MethodsThe study included 31 children with POTS and 27 healthy children from Peking University First Hospital between December 2013 and October 2015. A detailed medical history, physical examination results, and demographic characteristics were collected. Hemodynamics was recorded and the plasma SOwas determined.

ResultsThe plasma SOwas significantly higher in POTS children compared to healthy children (64.0 ± 20.8 μmol/L vs. 27.2 ± 9.6 μmol/L, respectively, P < 0.05). The symptom scores in POTS were positively correlated with plasma SOlevels (r = 0.398, P < 0.05). In all the study participants, the maximum heart rate (HR) was positively correlated with plasma levels of SO(r = 0.679, P < 0.01). The change in systolic blood pressure from the supine to upright (ΔSBP) in POTS group was smaller than that in the control group (P < 0.05). The ΔSBP was negatively correlated with baseline plasma SOlevels in all participants (r = -0.28, P < 0.05). In the control group, ΔSBP was positively correlated with the plasma levels of SO(r = 0.487, P < 0.01). The change in HR from the supine to upright in POTS was obvious compared to that of the control group. The area under curve was 0.967 (95% confidence interval: 0.928-1.000), and the cutoff value of plasma SOlevel >38.17 μmol/L yielded a sensitivity of 90.3% and a specificity of 92.6% for predicting the diagnosis of POTS.

ConclusionsIncreased endogenous SOlevels might be involved in the pathogenesis of POTS.

Characteristic chromatogram of Ligustri Lucidi Fructus which were processed by heat treatment with different temperatures and times was developed by HPLC. DPPH, ABTS and FRAP assays were performed to determine the antioxidant activity. The spectrum-effect correlation was studied using Partial Least Squares(PLS)to explore the active ingredients of Ligustri Lucidi Fructus by investigating the relationship between HPLC spectrum and antioxidant activity. S1, S2, S15, S24, S27, S29, S32, S33 and S35 were characteristic compounds in 35 matching characteristic chromatograms which were positive relationship with scavenging DPPH free radical activity. S1, S2, S5, S8, S16, S27 and S33 were significantly positively related to scavenge ABTS free radical activity. S12, S20, S22, S28, S30, S31, S32 and S34 were significantly positively related to restore Fe³⁺ activity. Among the chromatographic peaks, S1, S2, S27 and S33were positively related to scavenge DPPH free radical and ABTS free radical activity, and S32 was positively related to scavenge DPPH free radical and restore Fe³⁺ activity. S3, S19, S21, S22, S23, S33 and S34 were determined as salidroside, luteolin-7-O-glucoside, specnuezhenide, oleuropein, ligustroflavone, luteolin andapigenin, respectively. The results showed that although specnuezhenide and salidroside were stipulated index compounds to evaluate the quality of Ligustri Lucidi Fructus, the Ligustri Lucidi Fructus pharmcodynamic effect did not depend on the contents of those index components. The quality of traditional Chinese medicines(TCMs)should be determined by the compound groups associated with pharmcodynamic effect.

To study the heating treatment of Angelica dahurica under different temperature and time conditions on the stability of coumarins and tyrosinase activity. HPLC method was used to determine the contents of imperatorin and isoimperatorin, and tyrosinase activity was assayed by measuring the oxidation rate of L-DOPA in vitro. After heated, the contents of imperatorin increased. Expect for being heated at 90 ℃ for 2 h, the content of isoimperatorin was higher than crude one. Before and after being heated, A. dahurica showed an activating effect on tyrosinase. In the same temperature and time conditions, the activation rate increased with the rise of concentration of tyrosinase extracts. Heating process for A. dahurica could change the contents of imperatorin and isoimperatorin, mainly increasing their concentrations.

To improve a fast and high-quality isolation method for culturing the primary cardiomyocyte and fibroblast in vitro, the neonatal Wistar rats were decapitated accordingly and left ventricles were isolated under the sterile condition. The ventricles were chopped and digested in the enzyme solution containing 0.5 mg/mL type II collagenase. During this process, the digesting time, frequency and stirring speed, centrifuging frequency and speed were strictly controlled. The cardiomyocytes were separated from the cardiac fibroblast by using the Percoll density gradient centrifugation. The cell viability was tested by staining with 0.2% trypan blue. The purity of cardiomyocytes and fibroblasts were determined by immunoflourescent staining with anti-cTnI, anti-Vimentin and anti-α-SMA antibodies. The results indicated that with this protocol, the viability and purity of cardiomyocytes were 92% and 95%. The automobile pulse of the adhered cardiomyocyte was visible. For fibroblasts, the cell viability and purity were 96% and 94%. Our results demonstrate that this advanced isolation method is reproducible, and can simultaneously produce high-quality primary cardiomyocytes and fibroblasts for the future study.
Animals ; Cell Separation ; methods ; Cell Survival ; Centrifugation, Density Gradient ; Fibroblasts ; Heart Ventricles ; cytology ; Myocytes, Cardiac ; Povidone ; Rats ; Rats, Wistar ; Silicon Dioxide

Converting two poorly water-soluble crystalline drugs to co-amorphous drug systems by ball milling, quench-cooling, or cryo-milling method can improve stability of the drug, enhance dissolution rates, and reduce adverse reactions of the single drug. Co-amorphous system has been used to solve problems of co-administration of medicines. Formation and intermolecular interactions of co-amorphous drug systems may be verified by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Raman spectroscopy (RS) and Fourier transform infrared spectroscopy (FT-IR). Stability of co-amorphous drug systems is influenced by their glass transition temperature (Tg) and intermolecular interactions. The theoretical Tg values and the interaction parameter x are calculated by Gordon-Taylor equation and the Flory-Huggins equation, respectively. Thus, co-amorphous drug systems are analyzed theoretically at molecular level. Co-amorphous drug systems provide a new sight for the co-administration of medicines.
Calorimetry, Differential Scanning ; Chemistry, Pharmaceutical ; methods ; Cimetidine ; chemistry ; Drug Combinations ; Drug Compounding ; Drug Stability ; Glipizide ; chemistry ; Indomethacin ; chemistry ; Naproxen ; chemistry ; Ranitidine ; chemistry ; Simvastatin ; chemistry ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Spectrum Analysis, Raman ; Technology, Pharmaceutical ; methods ; Temperature ; X-Ray Diffraction

An efficient modified route based on the targeting mechanism of antibacterial fluoroquinolones for the shift from the antibacterial activity to the antitumor one was further developed. Using a fused heterocyclic ring, s-triazolothiadiazine as a carboxyl bioisostere of ciprofloxacin, the title compounds, 1-cyclopropyl-6-fluoro-7-piperazin-1-yl-3-(6-substituted-phenyl-7H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-3-yl)-quinolin-4(1H)-ones (5a-5e) and their corresponding N-acetyl products (6a-6e), were designed and synthesized, separately. Meaningfully, a ring-contraction of fused six-membered thiadiazine occurred by a sulfur extrusion reaction gave new tri-acetylated fused heterocycles related to pyrazolo[5, 1-c][1, 2, 4] triazoles (7a-7e). The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated for the synthesized fifteen heterocycles compared to parent ciprofloxacin by methylthiazole trazolium (MTT) assay. Interestingly, the results displayed that fifteen fused heterocyclic compounds showed more significant growth inhibitory activity (IC50 < 25.0 micromo x L(-1)) than that of parent ciprofloxacin (IC50 > 150.0 micromol x L(-1)), and the active order decreased from 7a-7e to 5a-5e to 6a-6e, respective.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; Cell Line, Tumor ; Ciprofloxacin ; pharmacology ; Cricetinae ; Cricetulus ; Fluoroquinolones ; chemical synthesis ; chemistry ; pharmacology ; HL-60 Cells ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; pathology ; Mice ; Structure-Activity Relationship ; Thiadiazines ; chemical synthesis ; chemistry ; pharmacology ; Triazoles ; chemical synthesis ; chemistry ; pharmacology