Correction to "Carboxymethyl Chitosan Oligosaccharide Holds Promise for Treatment of Stenosis Crohn's Disease".

[This corrects the article DOI: 10.1021/acsptsci.2c00035.].

Carboxymethyl Chitosan Oligosaccharide Holds Promise for Treatment of Stenosis Crohn's Disease.

Crohn's disease (CD) is a chronic intestinal disturbance mediated by mucosal immune hyperactivity that is often associated with the formation of stenosis. No reliable solution to stenosis CD exists so far. Therefore, we generated carboxymethyl chitosan oligosaccharide (CMCOS) as a new promising therapy and investigate its efficacy in an improved rat CD model. CMCOS was synthesized by enzymatic hydrolysis, and its biosafety was evaluated in vivo. The rat model of stenosis CD was optimized by an orthogonal experiment of 75 or 100 mg/kg trinitrobenzenesulfonic acid (TNBS) in a 50 or 75% ethanol enema. The therapeutic efficacy of CMCOS on the rat model of stenosis CD was investigated and compared with the commercial drug 5-aminosalicylic acid over a 28 day period of disease progression. The rat model of stenosis CD was well established by intracolonic administration of 75 mg/kg TNBS in 75% ethanol. CMCOS significantly alleviated CD symptoms morphologically, hematologically, and pathologically, promoting functional recovery of intestinal epithelium in a dose-dependent manner. CMCOS reduced infiltrations of inflammatory cells by regulating the IL-17A/PPAR-γ pathway and reduced fibro-proliferation and fibro-degeneration of the colon tissue by downregulating the TGF-ß1/WT1 pathway. 75 mg/kg TNBS in a 75% ethanol enema induces a rat model of stenosis CD suitable for preclinical pathology and pharmacological studies. The safety, antifibrosis, and functional repair performance of CMCOS make it a promising candidate for the treatment of stenosis CD.

Gas-Liquid-Solid Migration Characteristics of Gas Hydrate Sediments in Depressurization Combined with Thermal Stimulation Dissociation.

The exploitation of natural gas hydrate is always hindered by the migration of water and sands due to gas production. Depressurization combined with thermal stimulation is an effective method for hydrate dissociation. This paper reported the influence of gas-liquid-solid migration on morphological change of hydrate sediments in natural gas production using visualization method. Different backpressures combined with thermal stimulation methods were applied to simulate natural gas hydrate exploitation. Pressure compensation was first employed to study sediment recovery features. The expansion rate of a porous medium layer under combined dissociation and different backpressure (4.5, 3.5, 2.5, 1.5, and 0.1 MPa) was discussed. A 176% hydrate sediment expansion rate was found after the combined dissociation at 0.1 MPa. In addition, it was observed that the height of the water layer above the porous media after pressure compensation was gradually reduced with a decrease in backpressure and eventually disappeared at 0.1 MPa. It was also found that the disappearing water layer caused an anomalous memory effect phenomenon. Expansion and subsidence of sediments provide a better reference for hydrate exploitation and geological safety.

Cyclic Formation Stability of 1,1,1,2-Tetrafluoroethane Hydrate in Different SDS Solution Systems and Dissociation Characteristics Using Thermal Stimulation Combined with Depressurization.

Cold storage using hydrates for cooling is a high-efficiency technology. However, this technology suffers from problems such as the stochastic nature of hydrate nucleation, cyclic hydrate formation instability, and a low cold discharge rate. To solve these problems, it is necessary to further clarify the characteristics of hydrate formation and dissociation in different systems. First, a comparative experimental study in pure water and sodium dodecyl sulfate (SDS) solution systems was conducted to explore the influence of SDS on the morphology of the hydrate and the time needed for its formation under visualization conditions. Subsequently, the cyclic hydrate formation stability was investigated at different test temperatures with two types of SDS solution systems-with or without a porous medium. The induction time, full time, and energy consumption time ratio of the first hydrate formation process and the cyclic hydrate reformation process were analyzed. Finally, thermal stimulation combined with depressurization was used to intensify hydrate dissociation compared with single thermal stimulation. The results showed that the growth morphology of hydrate and the time required for its formation in the SDS solution system were obviously different than those in pure water. In addition, the calculation and comparison results revealed that the induction time and full time of cyclic hydrate reformation were shorter and the energy consumption time ratio was smaller in the porous medium. The results indicated that a porous medium could improve the cyclic hydrate formation process by making it more stable and by decreasing time and energy costs. Thermal stimulation combined with depressurization at different backpressures (0.1, 0.2, 0.3, and 0.4 MPa) effectively promoted the decomposition of hydrates, and with the decrease in backpressure, the dissociation time decreased gradually. At a backpressure of 0.1 MPa, the dissociation time was reduced by 150 min. The experimental results presented the formation and dissociation characteristics of 1,1,1,2-tetrafluoroethane hydrates in different systems, which could accelerate the application of gas hydrates in cold storage.

Benzo[a]pyrene induces oxidative stress and endothelial progenitor cell dysfunction via the activation of the NF-κB pathway.

Smoking is a major risk factor for atherosclerosis. In this study, we evaluated the effects of benzo[a]pyrene (BaP, a prominent component of tobacco smoke) on the function and pro-inflammatory response of human endothelial progenitor cells (EPCs). EPCs were isolated from umbilical cord blood and treated with different concentrations (10, 20 and 50 µmol/l) of BaP. The proliferation, migration, adhesion and angiogenesis of BaP-treated EPCs were evaluated using the cell counting kit-8 (CCK-8), Transwell assay, adhesion assay and in vitro tube formation assay, respectively. The activation of nuclear factor-κB (NF-κB) was evaluated by measuring the mRNA expression of NF-κB p65 and p50 by real-time RT-PCR and NF-κB translocation assay. Reactive oxygen species (ROS) production was determined by the reduction of fluorescent 2',7'-dichlorofluorescein diacetate (DCFH-DA). The results demonstrated that BaP treatment significantly inhibited the proliferation, migration, adhesion and angiogenesis of EPCs in vitro. In addition, BaP induced the release of interleukin (IL)-1ß and tumor necrosis factor-α from these cells. Moreover, the exposure of EPCs to BaP induced ROS generation and the activation of NF-κB. Experiments with EPCs pre-treated with pyrrolidine dithiocarbamate, an inhibitor of NF-κB, revealed that the BaP-mediated inhibition of proliferation, migration, adhesion and angiogenesis of EPCs is mainly regulated by NF-κB. Thus, tobacco smoke may induce oxidant-mediated stress responses in EPCs and impair their function via the activation of the NF-κB pathway.

Shengmai injection, a traditional chinese patent medicine, for intradialytic hypotension: a systematic review and meta-analysis.

Intradialytic hypotension (IDH) is a global public health problem. A rising number of IDH sufferers resort to Chinese patent medicine, Shengmai Injection (SMI) in China. The objectives of present study are to assess the effectiveness and safety of SMI as an adjunct therapy for IDH. A systematic search of 6 medical databases was performed up to December 2011. Randomized trials involving SMI adjuvant therapy versus conventional therapy were identified. RevMan 5.0 was used for data analysis. Ten randomized clinical trials with 437 participants were identified. Methodological quality was considered inadequate in all trials. Compared with conventional therapy, SMI adjunct therapy showed significant effects in improving the clinic effective rate (P < 0.01), decreasing the incidence of IDH episode (P < 0.01), decreasing the frequency of nursing interventions (P < 0.01), and increasing diastolic blood pressure (P < 0.01). There was no statistical significance in the improvement of mean arterial pressure (P = 0.22) and systolic blood pressure (P = 0.08) between two groups. Four studies had mentioned adverse events, but no serious adverse effects were reported in any of the included trials. In conclusion, SMI adjunct therapy appears to be potentially effective in treatment of IDH and is generally safe. However, further rigorous designed trials are needed.

Ablation of atrioventricular nodal reentrant tachycardia in a patient with reversal of slow and fast pathways inputs into the atrioventricular node.

We report a case of atrioventricular nodal reentrant tachycardia (AVNRT) coexistent with His bundle anomaly and atrial septal defects. The His-bundle potential was recorded at the coronary sinus (CS) ostium. Fractionated atrial potentials and an A:V electrogram ratio 1:3 were recorded at the anterior septum of the tricuspid annulus approximately 2 cm from CS ostium. Radiofrequency catheter ablation at the anterior septum of the tricuspid annulus effectively eliminated AVNRT.

Danshen protects endothelial progenitor cells from oxidized low-density lipoprotein induced impairment.

In this study, we examined the protective effects of Danshen both on endothelial progenitor cells (EPCs) in patients with hypercholesterolemia and on in-vitro EPCs of healthy volunteers. In the clinical study, we randomly divided 24 subjects with hypercholesterolemia into two groups (the control group and the Danshen-treated group). At the end of two weeks of treatment, the EPC cellular functions of both groups were tested. The results indicated that, compared to the control group, EPCs in the Danshen-treated group showed significantly better cellular functions, which was manifested in the cloning number, the proliferation capacity, the number of EPC adhesions, and cell migration. In the subsequent in-vitro experiments, EPCs were treated with vehicle, oxidized low-density lipoprotein (Ox-LDL, 100 microg/ml), or Ox-LDL (100 microg/ml) plus different concentrations of Danshen (Danshensu 2, 10, or 50 microg/ml, respectively) for 24 h. The results showed that Danshen treatments can prevent the detrimental effects of Ox-LDL on EPC cellular functions measured by proliferation capacity (0.24+/-0.08, 0.37+/-0.11, 0.30+/-0.04 vs. 0.13+/-0.02, P<0.05, P<0.01, and P<0.01, respectively), and adhesion ability (63.00+/-11.60, 70.00+/-10.80, 85.50+/-11.41 vs. 40.50+/-6.85, all P<0.01). Compared to the group treated with Ox-LDL alone, Danshen treatment significantly decreased the lipid peroxidation end product malondialdehyde (MDA) [(4.34+/-0.54), (3.98+/-0.47), (3.46+/-0.31) vs. (5.57+/-0.64) nmol/ml, all P<0.01], increased the production of superoxide dismutase (SOD) [(29.74+/-0.71), (31.09+/-0.83), (30.41+/-0.65) vs. (14.76+/-3.99) U/ml, all P<0.01], and lowered the expression of interleukin-6 (IL-6) [(24.62+/-7.69), (27.04+/-3.14), (33.38+/-18.86) vs. (230.67+/-33.53) pg/ml, all P<0.01] and tumor necrosis factor-alpha (TNF-alpha) [(41.72+/-6.10), (17.02+/-6.82), (3.73+/-2.26) vs. (228.71+/-41.53) pg/ml, all P<0.01] in Ox-LDL treated EPCs. These results suggest that Danshen may exert a protective effect through its antioxidant and anti-inflammatory features.

Carvedilol treatment ameliorates acute coxsackievirus B3-induced myocarditis associated with oxidative stress reduction.

Oxidative stress has been implicated in the pathogenesis of acute myocarditis. The imbalance between the occurrence of reactive oxygen species and the cellular antioxidant defense mechanism plays a key role in myocardial injury of viral myocarditis. Carvedilol, a nonselective beta-adrenoceptor antagonist with additional alpha1-adrenergic blocking and antioxidant properties, has been shown to be cardioprotective in experimental myocarditis. However, the expression of 4-hydroxy-2-nonenal (4-HNE), the most reliable marker of lipid peroxidation, has not been studied, and the antioxidative effects of carvedilol have not been investigated in the setting of acute viral myocarditis. This study was therefore designed to determine whether levels of lipid peroxides are elevated in the myocardium and whether carvedilol reduces the lipid peroxidation level and increases antioxidant enzyme activities. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol and metoprolol on 14-day survival rate, myocardial histopathological changes, cardiac function, the expression of 4-HNE, virus titers, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidases (GSH-Px) activities were studied. Lipid peroxidations including 4-HNE and MDA, were elevated in murine coxsackievirus-induced acute viral myocarditis. Carvedilol, but not metoprolol, improved survival, reduced lipid peroxidations including 4-HNE and MDA, and increased antioxidant enzyme activities including SOD and GSH-Px with amelioration of acute viral myocarditis. These results show that carvedilol but not metoprolol exerts some of its beneficial effects by inhibiting peroxidants.

[Effects of danshensu on function of EPCs which were damaged by Ox-LDL and study its possible mechanism].

OBJECTIVE: To observe the effects of danshensu on function of endothelial progenitor cells (EPCs) from peripheral blood which were damaged by oxidative low density lipoprotein (Ox-LDL). And study its possible mechanism. METHOD: Total mononuclear cells (MNCs) were isolated from peripheral blood by ficoll density gradient centrifugation, and were identified by demonstrating the expression of CD34, VEGFR-2 and AC133 with flow cytometry, to sure that all the cells needed were EPCs. Then the cells were plated on fibronectin-coated culture dishes. After incubation for 7 days, attached cells were collected and divided into three groups: Control group, Ox-LDL group, danshensu intervention group, stimulated with different cencentrations of danshensu (2, 10 and 50 mg x L(-1)), adhesion assay respectively. EPCs adhesion assay were performed by replating those on fibronectin-coated dishes, then adherent cells were counted. And take cell supernate of each group to carry on the SOD, MDA content examination. RESULT: Ox-LDL impaired EPC proliferative and adhesive capacity. In Ox-LDL group, The SOD content obviously drops, the MDA content obviously elevates. After danshensu interventing for 24 h, adhesive EPCs and migratory EPCs were significantly increased. Compared with Ox-LDL group, the SOD content of Danshensu intervention group obviously increased and the MDA content obviously reduced. CONCLUSION: danshensu could improve proliferative and adhesive capacity of EPCs that were impaired by Ox-LDL. The mechanism might relate to the oxidation resistance damage.

A case of massive pulmonary embolism with ST elevation in leads V1-4.

A 35-year-old man was referred to the emergency department after having a short syncopal episode while waiting for a Doppler scan of the lower extremities for a 4-week history of a painful right leg. He had no significant past medical history and was a non-smoker. On presentation he had severe chest pain and dyspnea associated with diaphoresis, and was hemodynamically unstable. His initial electrocardiogram (ECG) showed ST segment elevations in leads V(1-4), mimicking an anteroseptal myocardial infarction. However, the angiography showed the coronary arteries were normal and the right main pulmonary artery was partially occluded by large pulmonary emboli. The ECG changes were recorded in detail which also pointed to the diagnosis of pulmonary embolism (PE). This case shows how a PE can mimic an anteroseptal myocardial infarction on ECG, and the physiopathology of the ST elevation in PE was discussed.

[Effects of puerarin on expression of apelin and its receptor of 2K1C renal hypertension rats].

OBJECTIVE: To examine the change of puerarin on the expression of apelin and its receptor of the two-kidney, one-clip (2K1C) rats. METHOD: Tirty male Sprague-Dawley rats were randomly divided into normal control group (C), model group (M) and puerarin group (P). The mean of carotid arterial pressure (mCAP), mean of left ventricular end diastolic pressure (LVEDP), and the weight ratio of left ventricular mass (left ventricle plus septum) to bodyweight (LVM/BW) were measured to evaluate the model of 2K1C renal hypertension. The concentrations of apelin in the plasma and left ventricle (LV) were measured with radioimmunoassay. Apelin mRNA and APJ mRNA expressed in the LV were examined by reverse transcription-polymerase chain reaction (RT-PCR). The peptides of apelin and APJ expressed in the LV were detected with immunohistochemistry (IHC). RESULT: Compared with C group, the mCAP, LVEDP and LVM/BW of M group were higher 36.58%, 333.8% and 20.24%, respectively (P<0.05, P<0.01, P<0.01). Compared with M group, LVEDP and LVM/BW of P group were lower 65.24% and 13.12%, respectively (both P<0.05). However mCAP was of no significant difference between these two groups. The levels of apelin-36 in the plasma and LV of M group were respectively higher 18.56% and 207.38% than those of C group (both P<0.05), while ones of P group were lower 24.21% and 49.40% than those of M group (both P<0.05). The expressions of apelin mRNA and APJ mRNA at left ventricle tissues of 2K1C rats were higher 77.66% and 119.00% (both P<0.05) than those of C group. The ones of P group were lower 27.40% and 45.66% than those of M group (both P<0.01). The IHC results indicate that the expressions of apelin and APJ peptides at left ventricle tissues of 2K1C rats were higher 129.51% and 154.1% (both P<0.01) than those of C group, respectively. Whereas the ones of P group were lower 65.36% and 62.87% than those of M group (both P<0.01). CONCLUSION: Through regulating apelin/APJ system puerarin has protective effect on the development of left ventricular hypertrophy by renal hypertension.

Potassium channels: possible new therapeutic targets in Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and still remains incurable. New targets for potential pharmacological intervention should be explored and evaluated in order to slow down, delay or reverse the progress of this disease, and/or to avoid the serious side effects of levodopa praeparatum. Potassium (K+) channels widely express in basal ganglia and play crucial roles in the pathophysiology of PD, thereby raising their therapeutic application. Based on data from some pilot studies, we propose that K+ channels may provide possible new therapeutic targets for slowing down the progressive loss of dopamine neurons in PD. The most promising targets of K+ channels, including Kv, KATP, Kir, SK, and K2P channels, etc. deserve further pursuit for making comprehensive use of their novel therapeutic potential. Attempts to confirm this hypothesis may lead to new therapeutic strategy of PD.

[Inhibition of puerarin on pulmonary hypertension in rats with hypoxia and hypercapnia].

OBJECTIVE: To study the effects of puerarin on pulmonary Vascular remodeling in rats with pulmonary hypertension induced by chronic hypoxia and hypercapnia. METHOD: Forty male rats (180-220) g of grade two were randomly divided into five groups: normal control group (NC), hypoxia-hypercapnia 1, 2, 3 week groups (LH1, LH2, LH3) and hypoxia-hypercapnia 3-week + puerarin group (LHP3 group, puerarin intraperitoneal injection, 20 mg x kg(-1) x d(-1)). Collagen I, III and their mRNA were observed in pulmonary arterioles by the technique of immunohistochemistry and in situ hybridization. RESULT: Light microscopy showed media thickness of pulmonary arterioles was much higher in LH3 group than that of NC group, and, vessel cavity turned more straiter in LH3 group than that of NC group. Howerer, the damage of pulmonary arterioles in LHP3 group was much slighter than that of LH3 group. The levels of plasma ET-1 and lung homogenates Hyr and MDA were much higher in rats of LH3 group than those of NC group (P < 0.01), and lower in LHP3 group than LH3 groups (P < 0.01). The activities of SOD in lung homogenates were significantly lowered in hypoxic and hypercapnic groups compared with control group (P < 0.01), but higher in LHP3 group than that of LH3 group. Plasma NO content of group LH was lower than that of group NC (P < 0.01), it was highter in group LHP3 than that of group LH3 (P < 0.01). Expression of collagen I and collagen I mRNA in pulmonary arterioles were significantly higher in rats of LH groups than those of NC group (P < 0.01), and they were lower in rats of LHP3 group than those of LH3 group (P < 0. 01). Expression of collagen III and collagen III mRNA were not significant difference among three groups. CONCLUSION: Puerarin could improve pulmonary vascular remodeling in rats with pulmonary hypertension by inhibiting the deposition of collagen.

Contrast-enhanced sonographic characteristics of neovascularization in carotid atherosclerotic plaques.

PURPOSE: To evaluate neovascularization within carotid atherosclerotic plaques with contrast-enhanced sonography. METHODS: We used contrast-enhanced sonography to examine 63 patients with carotid atherosclerotic plaques. The features of neovascularization within the plaques were analyzed and correlated with plaque size and echogenicity. RESULTS: There were 81 atherosclerotic plaques, 62 of which (43 soft and 19 mixed) enhanced after injection of a contrast agent. The enhancement occurred from the carotid wall to the center of the plaque with a short-line pattern in 36 plaques, whereas 26 plaques enhanced from both the carotid wall and the carotid lumen, with a sparse spot pattern. The arrival time of contrast was shorter (p < 0.001) and time to peak was longer (p < 0.001) in the plaques than in the carotid lumen. Time to peak was shorter, whereas enhanced intensity was greater in soft plaques than in mixed plaques (p < 0.01 and p < 0.05, respectively). Among the 19 unenhanced plaques, 6 were hard, 3 were calcified, 3 were soft, and 7 were mixed. The thickness of the unenhanced plaques was <2.4 mm. CONCLUSION: Contrast-enhanced sonography allows the noninvasive, dynamic evaluation of neovascularization within carotid plaques, and the presence of neovascularization may correlate with plaque morphology.

[Effects of compound Salvia injection on number and activity of endothelial progenitor cells].

OBJECTIVE: To investigate the effects of Compound Salvia injection (CSI) on the number and activity of endothelial progenitor cells (EPCs). METHOD: Mononuclear fraction of human umbilical cord blood was obtained by density gradient centrifugation and plated on fibronectin coated culture dishes. Cells were divided in to five groups: group control, group VEGF, group CSI 50, group CSI 10 and group CSI 2 (supplemented with none cytokine, VEGF 10 ng x mL(-1), CSI 50, 10, 2 microg x mL(-1), respectively). After six days in culture, cell clusters were viewed with an inverted microscope, fluorescence-activated cell sorting (FACS) analysis of PE-CD34 and FITC-VE-Cadherin was performed to detect number of EPCs, adhesion assay was performed by replating cells on fibronectin coated dishes, and then counting adherent cells. RESULT: Numbers of EPCs of group VEGF, group CSI 10 and group CSI 2 were significantly increased as compared with those of group control ( P < 0.01, P < 0.05, P < 0.01, respectively), and numbers of EPCs of group CSI 2 were more than those of group CSI 10 and group V (P < 0.01). Compared with group control, number of EPCs of group CSI 50 was significantly decreased (P < 0.01). Compared with group control, numbers of clusters and adhesive EPCs of group CSI 10 and group CSI 2 were significantly increased, while those of group CSI 50 were significantly decreased. CONCLUSION: Low concentration CSI can significantly promote EPCs augmentation and enhance its functional activity, while high concentration CSI significantly restrains it.