Effect of different doses of atorvastatin on collateral formation in coronary artery disease patients with coronary atherosclerosis.

OBJECTIVE: The study aimed to explore the effect of different doses of atorvastatin on collateral formation in coronary artery disease (CAD) patients with coronary atherosclerosis. METHODS: The study included 218 CAD patients who received treatment between January 2017 and January 2020 at our hospital. They were assigned to the high-dose group (40 mg atorvastatin) and the low-dose group (20 mg atorvastatin) using the random table method with 109 patients per group. The blood lipid levels, TNF-α, hs-CRP, NO, and coronary atherosclerosis collateral formation before and after treatment in the two groups were compared, and favorable factors of good coronary artery collateral circulation were analyzed by multivariate logistic regression analysis. RESULTS: LDL-C, TG, and TC levels decreased, whereas HDL-C levels increased in the two groups after treatment. The high-dose group had lower LDL-C, TG, and TC levels but higher HDL-C levels than the low-dose group, and the difference was statistically significant ( P < 0.05). TNF-α and hs-CRP levels decreased while NO levels increased in both groups after treatment. The high-dose group had lower TNF-α and hs-CRP levels but higher NO levels than the low-dose group, and the difference was statistically significant ( P < 0.05). CONCLUSION: High-dose atorvastatin could blood lipid levels of modulate CAD patients and promote coronary atherosclerosis collateral formation. In addition, hypertension, LDL-C, HDL-C, TNF-α, hs-CRP, and NO were independent determinants of good coronary artery collateral circulation.

Spatial heterogeneity of soil nutrients in Yili River Valley.

Soil nutrients are a vital reference index of soil fertility and are essential in studying spatial variability for the development of land resources. The traditional statistical methods including correlation analysis and geostatistical analysis, were used to explore the spatial variability of nutrients and its influencing factors in the Yili River Valley. The results showed that soil total potassium (STK) had a weak variation, soil organic carbon (SOC), soil total nitrogen (STN) and soil total phosphorus (STP) showed a moderate degree of variation. Correlation analysis showed that SOC had a significant correlation with STN, STP, STK, silt, soil water content (SWC), Cos a and altitude (p < 0.01). In contrast, negative correlations were found between the SOC and sand, soil bulk density (SBD) and pH (p < 0.01), the same as STN. STP had a significant correlation with STK, silt (p < 0.01) and Cos a (p < 0.05), whereas negative correlations were found between the STP, sand and SBD (p < 0.01). STK had a significant correlation with silt, whereas negative correlations were found between the STK, sand and SBD. Ordinary Kriging interpolation showed that the distribution of SOC and STN had a high value in the northeast, northwest and southeast, and a low value in the central and southwest. STP was high in the northwest and southeast and low in the northeast and southwest. STK was high in the northwest and northeast and low in the central and southeast regions. This is helpful for the rational exploitation of land resources in ecological economy development in the Yili River Basin.

Pallidal volume reduction and prefrontal-striatal-thalamic functional connectivity disruption in pediatric bipolar disorders.

BACKGROUND: As a crucial node of the corticolimbic model, the striatum has been demonstrated in modulating emotional cues in pediatric bipolar disorders (PBD), the striatal distinction in structure and function between PBD-I and PBD-II remains unclear. METHODS: MRI data of 36 patients in PBD-I, 22 patients in PBD-II and 19 age-gender matched healthy controls (HCs) were processed. Here, we investigated structural and functional alterations of 8 subregions of striatum (bilateral nucleus accumbens, caudate, putamen and globus pallidus) by analyzing MRI data. RESULTS: We found volume reduction of the right pallidum, the significant positive correlation between the number of episodes and the functional connectivity between left pallidum and right caudate in PBD-I patients, abrupted prefrontal-striatal-thalamic functional connectivity in PBD-I group and decreased functional connectivity in PBD-II relative to HCs and PBD-I. LIMITATIONS: Future studies should enroll more subjects and adopt a longitudinal perspective, which could help to discover striatum structural or functional alterations during subject-specific clinical progress in different states. CONCLUSIONS: Results of the present study confirmed that structural and functional abnormality of striatum may be helpful in identifying PBD clinical types as distinctive biomarkers. The interruptions of the prefrontal-striatal-thalamic circuits may provide advantageous evidence for expounding the role of striatum in bipolar disorders etiology. Thus, potential mechanisms of dysfunction striatum need to be formulated and reconceptualized with multimodal neuroimaging studies in future.

Shared and specific patterns of structural and functional thalamo-frontal disturbances in manic and euthymic pediatric bipolar disorder.

Bipolar disorder (BD) is clinically defined by alternating depressive and manic episodes with a separated period of euthymia. Thalamo-frontal loop plays vital role in psychotic symptoms, altered motor control and executive difficulties in BD. It remains unclear that structural and functional alterations of thalamo-frontal loop among the different mood states in BD, especially in pediatric BD(PBD).Twenty manic PBD (mPBD), 20 euthymic PBD (ePBD) and 19 healthy controls (HCs) were included in the study. By analyzing the T1 images and fMRI signals, thalamus volume and frontal grey matter cortical thickness were tested, and functional connectivity (FC) between bilateral thalamus and frontal cortex was calculated. Relationship between clinical indices and thalamo-frontal FC was also evaluated in mPBD and ePBD adolescents.Compared to HCs, the cortical thickness of left middle frontal gyrus (MFG), bilateral superior frontal gyrus (SFG) was significantly decreased in both mPBD and ePBD patients, and volume of left thalamus and cortical thickness of right MFG significantly decreased in mPBD patients. Compared to that of the HCs and ePBD subjects, thalamo-frontal hyperconnectivity with MFG was found in mPBD, and compared with that of HCs, thalamo-frontal hypoconnectivity with precentral gyrus/SFG was found in ePBD. In ePBD patients, episode times positively correlated with FC values between thalamus and precentral gyrus.The findings of the present study demonstrate detailed knowledge regarding shared and specific structural and functional disruption in thalamo-frontal loop in mPBD and ePBD subjects. Thalamo-frontal abnormalities reported in adult BD subjects were also observed in adolescent BD patients, and thalamo-frontal dysfunction may be a crucial treatment target in BD.

Schisandrin Protects against Norepinephrine-Induced Myocardial Hypertrophic Injury by Inhibiting the JAK2/STAT3 Signaling Pathway.

Aims. Heart failure is closely associated with norepinephrine-(NE-) induced cardiomyocyte hypertrophy. Schisandrin is derived from the traditional Chinese medicine Schisandra; it has a variety of pharmacological activities, and the mechanism of schisandrin-mediated protection of the cardiovascular system is not clear. Main Methods. NE was used to establish a cardiomyocyte hypertrophy model to explore the mechanism of action of schisandrin. An MTT assay was used for cell viability; Hoechst fluorescence staining was used to observe the cell morphology and calculate the apoptosis rate. The cell surface area was measured and the protein to DNA ratio was calculated, changes in mitochondrial membrane potential were detected, and the degree of hypertrophic cell damage was evaluated. WB, QRT-PCR, and immunofluorescence were used to qualitatively, quantitatively, and quantitatively detect apoptotic proteins in the JAK2/STAT3 signaling pathway. Key Findings. In the NE-induced model, schisandrin treatment reduced the apoptosis rate of cardiomyocytes, increased the ratio of the cell surface area to cardiomyocyte protein/DNA, and also, increased the membrane potential of the mitochondria. The expression of both JAK2 and STAT3 was downregulated, and the BAX/Bcl-2 ratio was significantly reduced. In conclusion, schisandrin may protect against NE-induced cardiomyocyte hypertrophy by inhibiting the JAK2/STAT3 signaling pathway and reducing cardiomyocyte apoptosis.

Semiconducting polymer nano-PROTACs for activatable photo-immunometabolic cancer therapy.

Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency and off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way to modulate protein homeostasis for cancer therapy; however, the always-on bioactivity of existing PROTACs potentially leads to uncontrollable protein degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPNpro) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPNpro can remotely generate singlet oxygen (1O2) under NIR photoirradiation to eradicate tumor cells and induce immunogenic cell death (ICD) to enhance tumor immunogenicity. Moreover, the PROTAC function of SPNpro is specifically activated by a cancer biomarker (cathepsin B) to trigger targeted proteolysis of immunosuppressive indoleamine 2,3-dioxygenase (IDO) in the tumor of living mice. The persistent IDO degradation blocks tryptophan (Trp)-catabolism program and promotes the activation of effector T cells. Such a SPNpro-mediated in-situ immunometabolic intervention synergizes immunogenic phototherapy to boost the antitumor T-cell immunity, effectively inhibiting tumor growth and metastasis. Thus, this study provides a polymer platform to advance PROTAC in cancer therapy.

Organic Semiconducting Pro-nanostimulants for Near-Infrared Photoactivatable Cancer Immunotherapy.

In this study, an organic semiconducting pro-nanostimulant (OSPS) with a near-infrared (NIR) photoactivatable immunotherapeutic action for synergetic cancer therapy is presented. OSPS comprises a semiconducting polymer nanoparticle (SPN) core and an immunostimulant conjugated through a singlet oxygen (1 O2 ) cleavable linkers. Upon NIR laser irradiation, OSPS generates both heat and 1 O2 to exert combinational phototherapy not only to ablate tumors but also to produce tumor-associated antigens. More importantly, NIR irradiation triggers the cleavage of 1 O2 -cleavable linkers, triggering the remote release of the immunostimulants from OSPS to modulate the immunosuppressive tumor microenvironment. Thus, the released tumor-associated antigens in conjunction with activated immunostimulants induce a synergistic antitumor immune response after OSPS-mediated phototherapy, resulting in the inhibited growth of both primary/distant tumors and lung metastasis in a mouse xenograft model, which is not observed for sole phototherapy.

Phosphorus chemical speciation and seasonal variations in surface sediments of the Maowei Sea, northern Beibu Gulf.

This study presents the distribution, seasonal variations and factors influencing phosphorus (P) forms in surface sediments from the Maowei Sea. P forms were measured using the sequential extraction (SEDEX) procedures. Inorganic P (IP) was the predominant chemical form of total P (TP). Fe-bound P (FeP) was the main IP form. Sediment particle sizes, organic matter distribution, terrestrial input and aquaculture activity were responsible for the seasonal variations of different forms of P in sediment. In summer, the average proportions of P fractions in TP followed the order of organic P (OP) > Fe-P > authigenic P (CaP) > detrital P (De-P) > exchangeable P (Ex-P); in winter, the corresponding order was OP > Fe-P > De-P > Ca-P > Ex-P. The potential bio-available P accounted for 71.1 ±â€¯4.9% and 70.6 ±â€¯6.3% of TP in summer and winter, respectively. Sedimentary organic matter mainly came from land-based sources in winter.

Systems Pharmacology Based Strategy for Q-Markers Discovery of HuangQin Decoction to Attenuate Intestinal Damage.

The quality control research of traditional Chinese medicine (TCM) is lagged far behind the space of progress in modernization and globalization. Thus the concept of quality marker (Q-marker) was proposed recently to guide the quality investigations of TCM. However, how to discover and validate the Q-marker is still a challenge. In this paper, a system pharmacology based strategy was proposed to discover Q-marker of HuangQin decoction (HQD) to attenuate Intestinal Damage. Using this strategy, nine measurable compounds including paeoniflorin, baicalin, scutellarein, liquiritigenin, norwogonin, baicalein, glycyrrhizic acid, wogonin, and oroxylin A were screened out as potential markers. Standard references of these nine compounds were pooled together as components combination according to their corresponding concentration in HQD. The bioactive equivalence between components combination and HQD was validated using wound healing test and inflammatory factor determination experiment. The comprehensive results indicated that components combination is almost bioactive equivalent to HQD and could serve as the Q-markers. In conclusion, our study put forward a promising strategy for Q-markers discovery.

Amphiphilic semiconducting polymer as multifunctional nanocarrier for fluorescence/photoacoustic imaging guided chemo-photothermal therapy.

Chemo-photothermal nanotheranostics has the advantage of synergistic therapeutic effect, providing opportunities for optimized cancer therapy. However, current chemo-photothermal nanotheranostic systems generally comprise more than three components, encountering the potential issues of unstable nanostructures and unexpected conflicts in optical and biophysical properties among different components. We herein synthesize an amphiphilic semiconducting polymer (PEG-PCB) and utilize it as a multifunctional nanocarrier to simplify chemo-photothermal nanotheranostics. PEG-PCB has a semiconducting backbone that not only serves as the diagnostic component for near-infrared (NIR) fluorescence and photoacoustic (PA) imaging, but also acts as the therapeutic agent for photothermal therapy. In addition, the hydrophobic backbone of PEG-PCB provides strong hydrophobic and π-π interactions with the aromatic anticancer drug such as doxorubicin for drug encapsulation and delivery. Such a trifunctionality of PEG-PCB eventually results in a greatly simplified nanotheranostic system with only two components but multimodal imaging and therapeutic capacities, permitting effective NIR fluorescence/PA imaging guided chemo-photothermal therapy of cancer in living mice. Our study thus provides a molecular engineering approach to integrate essential properties into one polymer for multimodal nanotheranostics.

Dendronized Semiconducting Polymer as Photothermal Nanocarrier for Remote Activation of Gene Expression.

Regulation of transgene systems is needed to develop innovative medicines. However, noninvasive remote control of gene expression has been rarely developed and remains challenging. We herein synthesize a near-infrared (NIR) absorbing dendronized semiconducting polymer (DSP) and utilize it as a photothermal nanocarrier not only to efficiently deliver genes but also to spatiotemporally control gene expression in conjunction with heat-inducible promoter. DSP has a high photothermal conversion efficiency (44.2 %) at 808 nm, permitting fast transduction of NIR light into thermal signals for intracellular activation of transcription. Such a DSP-mediated remote activation can rapidly and safely result in 25- and 4.5-fold increases in the expression levels of proteins in living cells and mice, respectively. This study thus provides a promising approach to optically regulate transgene systems for on-demand therapeutic transgene dosing.

Quantitative Evaluation of the Compatibility Effects of Huangqin Decoction on the Treatment of Irinotecan-Induced Gastrointestinal Toxicity Using Untargeted Metabolomics.

Huangqin decoction (HQD), a traditional Chinese medicine (TCM), has been widely used to treat gastrointestinal syndrome in China for thousands of years. Chemotherapy drug irinotecan (CPT-11) is used clinically to treat various kinds of cancers but limited by its side effects, especially delayed diarrhea. Nowadays, HQD has been proved to be effective in attenuating the intestinal toxicity induced by CPT-11. HQD consists of four medicinal herbs including Scutellaria baicalensis Georgi, Glycyrrhiza uralensis Fisch, Paeonia lactiflora Pall, and Ziziphus jujuba Mill. Due to its complexity, the role of each herb and the multi-herb synergistic effects of the formula are poorly understood. In order to quantitatively assess the compatibility effects of HQD, mass spectrometry-based untargeted metabolomics studies were performed. The serum metabolic profiles of rats administered with HQD, single S. baicalensis decoction, S. baicalensis-free decoction and baicalin/baicalein combination were compared. A time-dependent trajectory upon principal component analysis was firstly used to visualize the overall differences. Then metabolites deregulation score and relative area under the curve were calculated and used as parameters to quantitatively evaluate the compatibility effects of HQD from the aspect of global metabolic profile and the specifically altered metabolites, respectively. The collective results indicated that S. baicalensis played a crucial role in the therapeutic effect of HQD on irinotecan-induced diarrhea. Both HQD and SS decoction regulated glycine, serine and threonine pathway. This study demonstrated that metabolomics was a promising tool to elucidate the compatibility effects of TCM or combinatorial drugs.

Urethral ultrasonography: A novel diagnostic tool for dysuria following bipolar transurethral plasma kinetic prostatectomy.

Urethral ultrasonography is non-invasive and able to indicate the urethral lumen clearly, as well as the surrounding tissues of the posterior urethra, without contrast agent or X-ray irradiation. In this paper, we evaluate the reliability of urethral ultrasonography in the diagnosis of dysuria following bipolar transurethral plasma kinetic prostatectomy (TUPKP). A total of 120 benign prostate hyperplasia (BPH) patients with dysuria undergoing TUPKP were enrolled in this study, with a mean age of 72.8 years. All the patients received urethral ultrasonography, urethroscopy and bladder neck urethra stenosis oulectomy. Among the 120 cases, there were 22 cases of bladder neck closure, 20 bladder orifice stricture, 60 urethral stricture, 10 prostate remnants, 2 calculi in prostatic urethra, 4 dysfunction of bladder detrusor muscle and 2 flap of internal urethral orifice. χ2-test was used for the comparison of ultrasonography and urethral cystoscopy in the diagnosis of dysuria following TRPKP, and no significant difference was found between two diagnostic tools (χ 2 = 0.94, P > 0.05). Urethral ultrasonography is a reliable and minimally invasive diagnostic tool for dysuria following TUPKP and is conducive to early treatment of dysuria following prostatectomy.

Immunomodulatory activity in vitro and in vivo of polysaccharide from Potentilla anserina.

The polysaccharide (PAP) from Potentilla anserina was evaluated for modulating effects by using mouse peritoneal macrophage and the immunosuppressed-model cyclophosphamide-induced. Phagocytotic and mononuclear phagocytic system function assays showed that PAP stimulated the phagocytosis of phagocyte. Splenocyte proliferation assay showed that PAP acted the effect combining Con A or LPS in splenocyte proliferation. The parameters detected showed that PAP increased thymus and spleen indices, the levels of LDH and ACP in the spleen, and IL-10 and IFN-γ in serum in immunosuppressed mice. The results suggest that PAP is involved in immunomodulatory effects leading to the exploration for PAP as a potential immunostimulant.

[Isolation and structure identification of flavonol glycoside from Lysimachia christinae Hance].

AIM: To isolate and prepare chemical standards. METHODS: Flavonol glycoside and rhamnonic acid gamma-lactone were isolated from whole plants of Lysimachia christinae Hance. with 95% ethanol and purified by silica gel column chromatography. UV, IR, MS, 1HNMR, 13CNMR, DEPT, HMQC, HMBC were used for the structural identification. RESULTS: Two compounds were obtained. They were identified as rhamnonic acid gamma-lactone (I) and kaempferol-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-xyloside (II). CONCLUSION: Compound I was isolated from this genus for the first time. Compound II is a new compound named as lysimachiin.

Clinical and experimental study of effect of Raondix Salviae Militiorrhiza and other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.

AIM:To study the effects of Radix Salviae Militiorrhiza (RSM), other blood-activating and stasis-eliminating Chinese herbs on hemodynamics of portal hypertension.METHODS:Portal pressure of cirrhotic dogs after chronic common bile duct ligation was measured directly; portal blood flow in patients with liver cirrhosis were detected by ultrasound Doppler.RESULTS:After administration of RSM and Radix Angelicae Sinensis (RAS) by intravenous infusion in cirrhosis dogs, the portal venous pressure (Ppv), wedge hepatic venous pressure (WHVP), hepatic venous pressure gradient (HVPG), were significantly decreased (P < 0.05-0.01), but the mean arterial pressure (MAP), and the heart rate (HR) remained unchanged. When nifedipine was used, Ppv, WHVP, MAP and HR were significantly decreased (P < 0.05), and the MVPG unchanged (P > 0.05). After administration of RSM, RSM+nifedipine and RSM+Hirudin+Nifedpin for 10-12 weeks, the diameter of portal vein (Dpv), spleen vein (Dsv), the portal venous flow (Qpv) and splenic venous flow (Qsv) in patients with hepatic cirrhosis were significantly lowered (P < 0.05-0.01), and the effect of RAS was weaker.CONCLUSIONS: The efficacy of decreasing Ppv by Chinese herbs RSM, RAS, etc. as compared with nifedipine, demonstrated that the Chinese herbs were slower in action than that of nifedipine, but more long-lasting and without side effects. Hence, long-term administration of Chinese herbs, would be more beneficial.