ObjectiveTo observe the clinical efficacy and safety of Tianmeng Lingjiao Formula（天礞羚角方， TLF） as an adjunctive therapy for paroxysmal atrial fibrillation （PAF） with phlegm-heat harassing the interior syndrome. MethodsNinety patients with PAF and phlegm-heat harassing the interior syndrome were enrolled and randomly assigned in a 2∶1 ratio to test group （60 cases） and control group （30 cases）. The control group received conventional western medicine， while the test group received TLF in addition to the conventional treatment， with one dose administered daily. The treatment course for both groups was 4 weeks. The efficacy of traditional Chinese medicine （TCM） syndrome and the rate of atrial fibrillation （AF） conversion were compared between groups. Assessments included AF burden， frequency and duration of AF episodes， TCM syndrome scores， and European Heart Rhythm Association （EHRA） AF symptom classification before and after treatment. Safety indicators such as blood routine， urine routine， stool routine， liver function， kidney function， and electrolytes were also monitored. Adverse events were recorded. ResultsA total of 82 patients completed the study （54 in the test group and 28 in the control group）. After treatment， AF burden， the frequency and duration of AF episodes， and TCM syndrome scores were significantly reduced in both groups， and the test group showed lower indicators than the control group （P＜0.01 or P＜0.05）. The AF conversion rate was 25.93% （14/54） in the test group， significantly higher than 3.57% （1/28） in the control group （P＜0.05）. The total effective rate for TCM syndrome efficacy was 83.33% （45/54） in the test group， which was significantly higher than 67.86% （19/28） in the control group （P＜0.05）. After treatment， the EHRA atrial fibrillation symptom severity in the test group showed significant improvement， and the improvement in atrial fibrillation symptoms was superior to that in the control group （P＜0.01or P＜0.05）. No significant abnormalities were observed in safety indicators， and no adverse events occurred during the trial. ConclusionTLF as an adjunctive therapy can reduce AF burden， enhance the conversion rate of AF， decrease the frequency and duration of episodes， and improve clinical symptoms in patients with paroxysmal atrial fibrillation presenting with phlegm-heat harassing the interior syndrome， with a favorable safety profile.

ObjectiveTo establish the characteristic sugar spectrum of polysaccharides， oligosaccharides and monosaccharides of wild-simulated and transplanted Astragali Radix， and find out the difference of the sugar spectrum between the two， so as to provide a basis for quality evaluation of Astragali Radix. MethodThe relative molecular weight distribution of polysaccharides from 18 batches of wild-simulated Astragali Radix and 12 batches of transplanted Astragali Radix were characterized by high performance liquid chromatography-evaporative light scattering detection（HPLC-ELSD） to establish the characteristic chromatograms of two kinds of polysaccharides. The difference in the peak area ratio of APS-Ⅱ， a polysaccharide component with a relative molecular weight of 10 kDa， in two kinds of Astragali Radix was analyzed， and the critical value of peak area ratio of APS-Ⅱ was determined by receiver operating characteristic（ROC） curve. At the same time， APS-Ⅱ was partially acid-hydrolyzed by trifluoroacetic acid（TFA） to establish characteristic spectra of two kinds of oligosaccharides from Astragali Radix based on HPLC-ELSD， and the characteristics of differential oligosaccharides were found by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Two kinds of APS-Ⅱ were completely acid-hydrolyzed by TFA and derivatized to establish characteristic spectra of two kinds of monosaccharides from Astragali Radix based on HPLC， PCA and OPLS-DA were performed on the peak area ratio of two kinds of monosaccharides to explore the differences in the composition of two kinds of APS-Ⅱ monosaccharides. ResultThe characteristic sugar spectrum of polysaccharides from Astragali Radix showed that the peak area ratio of APS-Ⅱ was the main difference， and the peak area of APS-Ⅱ of wild-simulated and transplanted Astragali Radix were 89.17%-97.17% and 80.14%-91.96%， respectively. The ROC curve determined the critical value of 92.28% for the difference of APS-Ⅱ peak area ratio of the two kinds of Astragali Radix. The multivariate analysis of APS-Ⅱ oligosaccharides revealed that the peak area ratio of oligosaccharides with polymerization degree≥10 was the main difference， which ranged from 11.835%-19.092% for wild-simulated products and 2.778%-7.017% for transplanted products. The results of monosaccharide characteristic sugar spectrum analysis showed that both Astragali Radix species consisted of six monosaccharides， and glucose and arabinose were the differential monosaccharide fractions. The peak area ratios of glucose and arabinose in wild-simulated products were 85%-93.9% and 2.7%-5.8%， respectively， while those of transplanted products were 74.3%-87.3% and 5.3%-10.7%， suggesting that the structures of the two polysaccharide fractions APS-Ⅱ of Astragali Radix may be different. ConclusionThe difference of sugar spectrum between two kinds of Astragali Radix may be related to the content and structure of APS-Ⅱ， and this study may provide a reference for the study of carbohydrates in Astragali Radix and the quality evaluation of medicinal materials.

The biofilms formed by pathogenic microorganisms seriously threaten human health and significantly enhance drug resistance, which urgently call for developing drugs specifically targeting on biofilms. Chitooligosaccharides extracted from shrimp and crab shells are natural alkaline oligosaccharides with excellent antibacterial effects. Nevertheless, their inhibition efficacy on biofilms still needs to be improved. Spirulina (SP) is a microalga with negatively charged surface, and its spiral structure facilitates colonization in the depth of the biofilm. Therefore, the complex of Spirulina and chitooligosaccharides may play a synergistic role in killing pathogens in the depth of biofilm. This research first screened chitooligosaccharides with significant bactericidal effects. Subsequently, Spirulina@Chitooligosaccharides (SP@COS complex was prepared by combining chitooligosaccharides with Spirulina through electrostatic adsorption. The binding of the complex was characterized by zeta potential, z-average size, and fluorescence labeling. Ultraviolet-visible spectroscopy (UV-Vis) showed the encapsulation efficiency and the drug loading efficiency reached up to 90% and 16%, respectively. The prepared SP@COS2 exhibited a profound synergistic inhibition effect on bacterial and fungal biofilms, which was mainly achieved by destroying the cell structure of the biofilm. These results demonstrate the potential of Spirulina-chitooligosaccharides complex as a biofilm inhibitor and provide a new idea for addressing the harm of pathogenic microorganisms.
Humans ; Spirulina ; Anti-Bacterial Agents/chemistry* ; Chitosan/pharmacology* ; Biofilms ; Chitin/pharmacology*

COVID-19 represents the most serious public health event in the past few decades of the 21^st century. The development of vaccines, neutralizing antibodies, and small molecule chemical agents have effectively prevented the rapid spread of COVID-19. However, the continued emergence of SARS-CoV-2 variants have weakened the efficiency of these vaccines and antibodies, which brought new challenges for searching novel anti-SARS-CoV-2 drugs and methods. In the process of SARS-CoV-2 infection, the virus firstly attaches to heparan sulphate on the cell surface of respiratory tract, then specifically binds to hACE2. The S protein of SARS-CoV-2 is a highly glycosylated protein, and glycosylation is also important for the binding of hACE2 to S protein. Furthermore, the S protein is recognized by a series of lectin receptors in host cells. These finding implies that glycosylation plays important roles in the invasion and infection of SARS-CoV-2. Based on the glycosylation pattern and glycan recognition mechanisms of SARS-CoV-2, it is possible to develop glycan inhibitors against COVID-19. Recent studies have shown that sulfated polysaccharides originated from marine sources, heparin and some other glycans display anti-SARS-CoV-2 activity. This review summarized the function of glycosylation of SARS-CoV-2, discoveries of glycan inhibitors and the underpinning molecular mechanisms, which will provide guidelines to develop glycan-based new drugs against SARS-CoV-2.
Antibodies, Neutralizing ; Glycosylation ; Heparin ; Heparitin Sulfate ; Humans ; Polysaccharides/chemistry* ; Receptors, Mitogen/metabolism* ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism* ; COVID-19 Drug Treatment

Objective:To evaluate the feasibility and safety of total aortic arch surgery under mild hypothermicvia single upper hemisternotomy approach.Methods:From January 2019 to July 2019, 35 patients(31 male and 4 female) with Stanford A type aortic dissection were diagnosed, who were(43.7±5.7)years old. Aortic arch surgeries were carried out under mild hypothermic via single upper hemisternotomy approach and the perioperative mortality, time of cardiopulmonary bypass(CPB), aortic cross clamp(ACC), circulation arrest(CA) and morbidity of neurological dysfunction were respectively were recorded.Results:All patients were finished aortic arch surgery under mild hypothermic single upper hemisternotomy approach, with 8.6% of mortality(3 patients died perioperation). The time of CPB, ACC and CA were respectively(202±53)min, (128±28)min and(8±3)min. There were 6 cases of transient neurological dysfunction(17.1%) and 1 case of permanent neurological dysfunction(2.9%).Conclusion:Aortic arch surgery under mild hypothermic for Standford A dissectionvia single upper hemisternotomy approach is safe and feasible.

The inhibitory effect of NACOS on dyslipidemia and potential molecular mechanisms by in vitro and in vivo experiments were investigated. For in vitro study, four experimental groups were designed by using HepG2 cells, including the control group, palmitic acid (PA) treatment alone group, NACOS treatment alone group and NACOS + PA treatment group. For in vivo study, male C57BL/6 mice were divided into four groups (n=5) at random including the normal control group (NCD), high fat diet (HFD) group, NACOS treatment alone group, NACOS+HFD group, which were treated for 20 weeks. The used methods in this study were as follows: the observation of lipid droplet deposition in HepG2 cells by oil red O staining, the detection of mRNA levels of lipid metabolism-related regulators and inflammatory cytokine by RT-PCR method, the monitoring of MAPKs and PI3K/Akt pathway activation by Western blotting method. The in vitro study shows that, NACOS had no toxicity on the viability of HepG2 cells at 25-100 μg/mL and significantly reduced the deposition of lipid droplet. Also, based on both in vitro and in vivo investigation, NACOS evidently down-regulated the expression of lipid metabolism-related regulators (PGC1α, Cox5b, Mcad) and inflammatory cytokine (IL-1β) at mRNA level (P<0.05 or 0.01), and suppressed the activation of p38, ERK1/2 and Akt in HepG2 cells and lever tissues from HFD-fed mice (P<0.05 or 0.01). Based on the above, NACOS may inhibit the oxidation of liver mitochondrial fatty acid and the lipid biosynthesis, block the inflammatory responses and prevent the HepG2 cells and C57BL/6 mice from lipidemia.

Objective To investigate the role of calpain in the spinal dorsal horn in development of paw inflammatory pain in rats.Methods Forty-eight male SD rats,aged 6 weeks,weighing 160-200 g,were randomly divided into three groups:normal control group(group C,n =8),PBS group( n =16),zymosan-induced paw inflammatory pain group (group Z,n =24).Inflammatory pain was induced by injection of zymosan 1.25 mg into the plantar surface of left hindpaw.Group PBS received the equal volume of PBS 100 μl.The mechanical paw withdrawal threshold (MWT),paw withdrawal thermal latency (PWTL) and maximum thickness of the plantar surface of left hindpaw were measured before (T0 ) and at 30 min,1,2,4,8,24 and 48 h(T1-7 ) after zymosan or PBS injection.Eight rats were sacrificed at T4 in group PBS and at T4.6,7 in group Z respectively.The left lumbar segment (L4-6) was removed to determination of spectrin α Ⅱ breakdown products,IκBα,cyclooxygenase-2 (COX-2)expression and NF-κB activity in the spinal dorsal horn by Western blot.Results Compared with group C,MWT and PWTL were significantly decreased,maximum thickness of paw and NF-κB activity in the spinal dorsal horn were significantly increased,spectrin α Ⅱ breakdown products and COX-2 expression in the spinal dorsal horn were upregulated,while IκBα expression was down-regulated in group Z( P ＜ 0.05 or 0.01 ),but no significant change was found in group PBS( P ＞ 0.05).Conclusion The activation of calpain in the spinal dorsal horn is involved in the development of paw inflammatory pain in rats through activating NF-κB and up-regulating the expression of COX-2.

Objective To review the experience and early clinical results of eversion carotid endartotectomy (eCEA) in treatment of patients with symptomatic carotid stenosis. Methods eCEA were performed on 32 patients who suffered from the extracranial carotid stonosis. The treatment results were retrospectively reviewed. Results Thirty-two patients were successfully treated with eCEA. The symptom in 17 patients with transient ischemia attach (TIA) admitted to hospital did not recurrence, the other original symptoms of the patients had different degrees of improvement or disappeared. Two patients had TIA during 72 h after surgery, but 24 h repeatedly CTA examination without infarcts oecurring, and recovered after the treatment of small doses of urokinase. Two cases of severe swelling appeared tracheal shift incision, and went smoothly through edema by treatment of tracheal intubatian. In 4 patients headache reliefed in 2-3 d after medical treatment of the dehydration. Seven patients appeared different degree of hoarseness, and got recovery through neurotrophic medication for 1 month. No other serious complication occurred. Follow-up by 6 months, no CTA carotid artery stenosis appeared again. Conclusion eCEA is an effective method to treat symptomatic carotid stenosis.

Objective To investigate the effect of ketamine pretreatment on acute tolerance to morphine in rats with chronic inflammatory pain.Methods Twenty-four adult male SD rats weighing 180-200 g were randomly divided into 3 groups (n=8 each): group Ⅰ morphine (M) ,group Ⅱ ketamine (K) and group Ⅲ ketamine + morphine (KM). Chronic inflammatory pain was induced by subcutaneous injection of Freund's adjuvant 0.125 ml into the plantar surface of left hindpaw. Three days after Freund's adjuvant injection, the animals received intraperitoneal (IP) morphine 5 mg/kg in group M, IP ketamine 10 mg/kg in group K or IP ketamine 10 mg/kg 10 min before IP morphine 5 mg/kg in group KM once a day for 3 consecutive days respectively. The paw withdrawal threshold to yon Frey hair stimulation (PWT) and paw withdrawal latency to noxious thermal stimulation(PWLT) using the hot plate test were measured before Freund's adjuvant injection (T0, baseline), and every day before (T1) and at 15 (T2), 30 (T3), 60 (T4) and 120 min (T5) after medication for 3 days (D1,2,3).Results PWT was significantly increased after medication on D1,2,3 in group KM but only on D1,2 in group M. PWLT was significantly prolonged after medication on D1,2,3 in group KM but only on D1 in group M. Conclusion Ketamine 10 mg/kg pretreatment can decrease the acute tolerance to morphine in rats with chronic inflammatory pain.

AIM: To investigate if pregabalin could depress the acute tolerance induced by morphine when curing the chronic inflammatory pain of rats.METHODS: 24 adult male Sprague-Dawley rats weighing 180-200 g were randomly divided into three groups(8 in each group).Freund's adjuvant was injected subcutaneously in left hind-paw of the rat to establish the chronic inflammatory pain model.3 days later,rats received 3 daily intragastrical(p.o.) morphine 8 mg/kg(M group),pregabalin 3 mg/kg(P group) or morphine 8 mg/kg+pregabalin 3 mg/kg(MP group) administrations respectively.The rats' pressure-withdrawal threshold(PWT) and paw withdrawal thermal latency(PWTL) were determined with Von-Frey hair test and rat hot-plate test respectively.The results of PWT and PWTL before and 15,30,60,120 min after medication were recorded.RESULTS: PWT and PWTL of the rats in M group increased after medication on all the time points of the first day and 15 min of the second day(P