Objective To determine the effects of practicing a simplified 24 movement form of Tai chi on the level of inflammatory cytokines and the quality of life of type 2 diabetes patients. Methods A group of type 2 diabetes patients practiced a simplified 24 movement Tai chi routine 60 min/d, 3 d/week for 6 months. Plasma glu-cose and insulin concentration were monitored. The plasma level of IL-6, IL-18, sCD40L, hsCRP and HBAc1 were measured. Changes in the patients' quality of life were also measured by using the SF-36. Results Serum IL-6,IL-18, hsCRP and sCD40L levels were all significantly lower compared with a control group. Significant quality of life improvements were seen in the Tai chi group compared with the controls. Significant reductions were seen in blood pressure, glycated haemoglobin, glucose, insulin resistance and urinary albumin. Conclusions These results sug-gest that regular Tai chi practice can prevent complications and improve the quality of life of diabetes sufferers through glyeaemic control and down-regulating inflammatory cytokine levels.

Objective To investigate the effect of imbedding chemotherapy of sustained release of 5-fluorouracil on the healing of colonic stoma in dog. Methods Twenty-eight adult hybrid dogs were randomly divided into chemotherapy group (n=22) and control group (n=6). The canine sigmoid colon were firstly detached and then anastomosed via median abdominal incision, 200 mg sustained release of 5-fluorouracil was imbedded in the mesentery 1.0-1.5 cm away from colonic stoma in chemotherapy group, whereas the control substance was injected into the dogs in control group. Tissue samples were collected from mesentery and stomas on 3, 5, 7, 10 and 15 days after operation, respectively, in order to observe the healing of stoma. The drug concentrations in the stoma and in the tissues that were 0, 1, 3, 5, 7, 10 and 15 cm away from the imbedding point were also measured by high performance liquid chromatography method at different phases. Results The tissues from colonic stoma only showed inflammatory reaction at early stage, with no necrosis and cellular degeneration. It was observed that the stoma healed basically on the tenth day after operation. The drug concentrations in the tissues gradually decreased at the range of 0-15 cm over time, but all of which were higher than the anti-tumor effective concentration (0.10 ?g/g). Conclusion The imbedding chemotherapy of sustained release of 5-fluorouracil in mesentery has little effect on the healing of stoma, and it could remain an effective anti-tumor concentration in a period of time.

Aim To study the effects of sodium ferulate on A?induced cognitive deficits and expressions of IL-1? and phospho-p38MAPK proteins.Methods Alzheimers disease model of rats was produced by intracerebroventricular injection of A?_(25-35)(10 ?g,once).Morris water maze was used to measure spatial memory performance.Nissl staining and immunohistochemical technique for glial fibrillary acidic protein(GFAP) were employed to determine the morphology of pyramidal neurons and astrocyte infiltration in hippocmpal CA1 regions.The levels of phospho-p38MAPK and IL-1? were determined by Western blot and ELISA method.Reverse transcription-PCR analysis showed changes in FasL mRNA.Results Intracerebroventricular injection of A?_(25-35)in rats resulted in spatial memory impairments shown by longer escape latency and decreased percentage of time spent in the target quadrant.These behavioral dysfunctions were accompanied by astrocyte activation and infiltration,increased IL-1? production and elevated FasL mRNA level,the loss of pyramidal neurons in hippocampal CA1,and the increase of phosphorylated p38MAPK.Oral administration of sodium ferulate(50,100,250 mg?kg~(-1)daily) and ibuprofen 15 mg?kg~(-1)daily markedly improved the memory impairment,attenuated pyramidal neuronal damage,and reversed the A?-induced increases in IL-1? and p38MAPK activation.Conclusion sodium ferulate prevents A?-induced neurotoxicity through suppressions of inflammatory response and the activation of p38MAPK.

AIM To explore the mechanism of amyloid β-protein fragment 25-35(Aβ25-35)-induced inflammation and apoptosis in rat hippocampus in vivo by studying mitogen-activated protein kinase (MAPK) signaling pathway and the protective effect of anti-inflammatory drug ibuprofen. METHODS Rats were given ibuprofen (7.5 mg·kg-1 daily, ig) for 3 weeks prior to and 1 week after icv single dose of Aβ25-35 (10 μL, 1 mmol·L-1). Seven days after injection, Nissl staining and immunocytochemical technique were employed to determine the morphology of pyramidal neurons and astrocyte infiltration in hippocampal CA1. The expressions of IL-1β, extracellular signal-regulated kinase (ERK), p38 MAPK, PKC, and caspase-3 were determined by Western blot. Reverse transcription-PCR analysis showed changes in IL-1β mRNA level. RESULTS Intracerebroventricular injection of Aβ25-35 elicited astrocyte activation and infiltration and caused a strong inflammatory reaction characterized by increased IL-1β production and elevated IL-1β mRNA level. The inflammatory reaction was accompanied by the loss of pyramidal neurons in hippocampal CA1. The phosphorylation of p38 MAPK was significantly increased, on the other hand, the phosphorylation of ERK was significantly reduced and these were coupled with the increase of caspase-3 expression in hippocampal CA1. Ibuprofen (7.5 mg·kg-1 daily, 4 weeks) significantly reduced Aβ-induced IL-1β expression, caspase-3 expression and p38 MAPK activation. The loss of pyramidal neurons was also significantly attenuated by treatment with ibuprofen. CONCLUSION The activation of p38 MAPK and the down-regulation of ERK play a pivotal role in the inflam-matory response and apoptosis evoked by Aβ25-35 in vivo, which can be prevented by ibuprofen.

Objective To investigate the role of mesenchymal stem cells in the repair of radiation induced liver injury.Methods 12 female SD rats were irradiated with 20 Gy 6 MV X-rays on the right lobe of the liver,to establish the model of radiation induced liver injury.The rats were divided randomly into two groups as invention group and control group,and transplanted with 1 ml male mesenchymal suspension or 1 ml normal saline in 4 hours after radiotherapy.The morphological changes of liver were observed.The existence of sex determining gene Y(SRY)and the level of alpha-smooth muscle actin (a-SMA) were detected.Results Some injury of right lobe liver in two groups were observed,and the injury degree of right lobe liver in intervention group were lower than that of control group.The amount of SRY positive cells in the right lobe liver of intervention group was higher than that in the left lobe liver(t ＝ 3.77,P ＜0.05).The positive expression rate of a-SMA in right lobe liver of intervention group was lower than that of control group.Conclusions Acute radiation induced liver injury could lead BMSCs＇ homing in order to decrease the degree of liver fibrosis.

Objective To quantify the amplitudes of lung tumor motion during free-breathing using four dimensional computed tomography (4DCT), and seek the characteristics of tumors with large motion. Methods Respiratory-induced tumor motion was analyzed for 44 tumors from 43 patients. All patients un-derwent 4DCT during free-breathing before treatment. Gross tumor volumes (GTV) on ten respiratory phases were contoured by the same doctor. The eentroids of GTVs were autoplaeed with treatment software (ADAC Pinnacle 7.4f), then the amplitudes of tumor motion were assessed. The various clinical and anatomic fac-tors associated with GTV motion were analyzed. The characteristics of tumors with motion greater than 5 mm in any direction were explored. Results The tumor motion was found to be associated with T stage, GTV size, the superior-inferior (SI) tumor location in the lung, and the attachment to rigid structures such as the chest wall, vertebrae or mediastinum. The motion over 5 mm was observed in ten tumors, which were all lo-cated in the lower or posterior half of the lung, with the greatest motion of 14.4 mm. For 95% of the tumors, the magnitude of motion was less than I 1.8 mm, 4.6 mm and 2.7 mm along the SI, anterior-poste-rior (AP) and lateral directions, respectively. Conclusions Tumor motion due to breathing is associated with tumor location, volume, and T stage. The greatest motion was in the SI direction for unfixed tumor in lower-lobe, followed by tumor in upper-lobe posterior-segment.

Objective To summarize the manifestation of solid pseudopapillary tumor of the pancreas (SPTP) on ultrasound and contrast-enhanced ultrasound (CEUS) and to investigate the diagnostic value of CEUS. Methods The ultrasound and CEUS images of six patients with SPTP confirmed by pathology were reviewed. According to CEUS record,the enhanced and wash-out time,enhanced speed and degree of tumor were analyzed. Results On ultrasound, SPTP presented as solid, well-circumscribed masses, usually heterogeneous in echo texture, and some of them contained macro-calcification. On CEUS, the tumor enhanced simultaneously or slightly late compared with normal pancreatic tissues. The contrast agent washed out quickly in all tumors than in normal pancreatic tissues. The enhanced degrees were equal to or less than that of the normal pancreatic tissues. Some tumors showed capsule and septum enhancement. Conclusions The manifestation of SPTP on CEUS had some features and may be helpful for differentiation diagnosis combine with ultrasound.

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

AIMTo determine whether activation of kappa-opioid receptor with U50,488H, a selective kappa-opioid receptor agonist, produces any changes in electrical uncoupling during prolonged ischemia and whether these changes in electrical uncoupling is associated with the cardioprotection induced by kappa-opioid receptor activation, and to explore the possible mechanism.

METHODS(1) To observe the effect of U50,488H (10(-7), 10(-6), 3 x10(-6) and 10(-5) mol/L), a selective kappa-opioid receptor agonist, or with a selective kappa-opioid receptor antagonist nor-BNI (5 x 10(-6) mol/L), or with a mitochondrial K(ATP) channel inhibitor 5-HD on myocardium during ischemia/reperfusion in isolated perfused rat heart. Parameters of measurements include hemodynamic data, formazan content, heart rate, coronary flow, and lactate dehydrogenase (LDH). (2) To examine the effect of U50,488H of different concentration on electrical coupling parameters (including onset of uncoupling, plateau time, slope, and fold increase in r1) during 70 min myocardial ischemia in isolated perfused rat heart.

RESULTS(1) Pretreatment with U50,488H concentration dependently increased formazan content and reduced LDH release induced by 30 min of ischemia and 120 min of reperfusion. (2) The onset of electrical uncoupling and plateau time during prolonged ischemia was delayed by kappa-opioid receptor activation with U50,488H. (3) Linear regression analysis shown that the increase in formazan content and decrease in LDH release produced by kappa-opioid receptor activation was associated with delayed electrical uncoupling during prolonged ischemia. (4) The effects of U50,488H on formazan content, LDH release and on electrical coupling were abolished by nor-BNI, or 5-HD.

CONCLUSIONThis results demonstrate that the onset of electrical uncoupling during prolonged ischemia is delayed by kappa-opioid receptor activation with a selective kappa-opioid receptor agonist U50,488H, and that delayed electrical uncoupling is associated with the cardioprotection induced by kappa-opioid receptor activation with U50,488H. These effects of kappa-opioid receptor activation with U50,488H are mediated by mitochondrial K(ATP) channels.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Animals ; Antihypertensive Agents ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; Male ; Myocardial Ischemia ; physiopathology ; Myocardium ; metabolism ; Naltrexone ; analogs & derivatives ; pharmacology ; Potassium Channels ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; agonists

Objective To analyze the efficacy and safety of losartan in the treatment of massive proteinuria in kidney transplant recipients.Methods All of the 82 patients were randomized in two groups:losartan group and control group(amlodipine group).Both of the groups were divided into two different subsets according to blood pressure control Twenty-four-hour proteinuria,serum creatinine,blood pressure and adverse effects were observed.Results Losartan and amlodipine had the similar effects on blood pressure control The 24-h proteinuria in losartan group at the end of the study was significantly lower than that at the baseline,and there was significant difference between the losartan blood pressure control subset and the losartan blood pressure un-control subseL The effective rate and significant effective rate in losartan group for massive proteinuria were higher than in control group.Conclusion T Losartan can be effectively and safely used for the treatment of massive proteinuria in renal transplant recipients independent of blood pressure.