OBJECTIVETo observe the effect of Feiyanning Granule (FYN) on tumor growth and cell cycle distribution in mice with Lewis lung cancer, as well as its influence on G1/S cell cycle checkpoint dominating signaling RB-E2F1 bio-axis.

METHODSModeled C57BL/6 mice were randomly divided into 6 groups: the model group (A), the DDP treated group (B) peritoneally injected with cisplatin 0.1 mg on d1, d3 and d5 after modeling, and the 4 FYN treated groups (C-F), administered via gastrogavage with FYN Decoction, and FYN Granule in small-, median- and high- dose respectively for 14 days. The tumour inhibiting rate, tumour weight, and body weight of mice were observed after treatment; cell cycle distribution was detected by flow cytometry (FCM), RB-E2F1mRNA expressions in tumour tissue were analyzed by RT-PCR, and their protein expressions by Western blot.

RESULTSTumour weight in the 5 treated groups was lower than that in the model group (P < 0.05, P < 0.01). Body weight in group E was significantly higher than that in group A and B (P < 0.05, P < 0.01). FCM analysis showed the proportion of G0/G1 phase was higher in group E than in group A, B and C (P < 0.01), and cancer cell proliferation index (PI) in group E was lower than in group B (P < 0.05, P < 0.01). RT-PCR showed mRNA level of E2F1 was lower, but that of RB was significantly higher in group E than those in group A, B and C respectively (P < 0.01). Westem blot analysis showed the protein expression of E2F1 was lower in group E and B than that in group A (P < 0.05), while the protein expression of Rb in group E was higher than that in group A, B and C (P < 0.05).

CONCLUSIONThe effect of FYN in inhibiting Lewis lung cancer growth was related to its intervention on cancer cell cycle distribution which blocks most tumor cells in G0/G1 phase. Moreover, FYN can reduce MDM2 expression, enhance P53 expression to influence cell cycle G1/S checkpoint dominating signaling, so as to achieve the effect of antagonizing lung cancer cell proliferation.

Animals ; Carcinoma, Lewis Lung ; metabolism ; pathology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction ; drug effects

COVID-19 epidemic continues to spread around the world till these days, and it is urgent to develop more safe and effective new drugs. Due to the limited P3 biosafety laboratories for directly screening inhibitors of virulent viruses with high infectivity, it is necessary to develop rapid and efficient screening methods for viral proteases and other related targets. The main protease (M^pro), which plays a key role in the replication cycle of SARS-CoV-2, is highly conserved and has no homologous proteases in humans, making it an ideal target for drug development. From two different levels, namely, molecular level and cellular level, this paper summarizes the reported screening methods of SARS-CoV-2 M^pro inhibitors through a variety of representative examples, expecting to provide references for further development of SARS-CoV-2 M^pro inhibitors.

As a common protease with high similarity among coronavirus species, the main protease (M^pro) of SARS-CoV-2 is responsible for the catalytic hydrolysis of viral precursor proteins into functional proteins, which is essential for coronavirus replication and is one of the ideal targets for the development of broad-spectrum antiviral drugs. This paper reviews the main protease inhibitors of SARS-CoV-2, including their molecular structures, potencies and drug-like profiles, binding modes and structure-activity relationships, etc.

OBJECTIVETo study the sterilizing effect and mechanism of electrolyzed-oxidizing water (EOW) and electrolyzed-reductive water (ERW) for Bacillus subtilis var. niger (ATCC9372) and Escherichia coli (8099).

METHODSThe generations of EOW and ERW were made in the ion membrane electrolysis cell. The sterilization manner was the suspension quantitative germicidal test.

RESULTSThe killing rate of EOW for Bacillus subtilis var. niger was 99.59% in 30 minutes and the killing logarithm value was 2.38 log cfu/ml; the killing rate of ERW for Bacillus subtilis var. niger was 94.62% in 60 minutes and the killing logarithm value was 1.27 log cfu/ml; the killing rate of ERW for Escherichia coli was 100% in 30 minutes and the killing logarithm value was 8.26 log cfu/ml. When the available chlorine content (ACC) value in EOW was 74.90 mg/L and killing time was 30 minutes, the killing rate for Bacillus subtilis var. niger was 99.89% and the killing logarithm value was 2.67 log cfu/ml. When the ACC value was 6.82 mg/L, the killing rate for Bacillus subtilis var. niger was 83.30% and the killing logarithm value was 0. 78 log cfu/ml under the same time. When the oxidizing-reductive potential (ORP) and pH values of EOW were 1138 mV and 2.24 respectively, the killing rate for Bacillus subtilis var. niger was 99.99%. When the ORP and pH values of EOW were 883 mV and 5. 43 respectively, the killing rate of Bacillus subtilis var. niger was 99.73%. When the ORP value of ERW is -918 mV, the sterilizing rate for Bacillus subtilis var. niger was 94.62%; when the ORP value is -155 mV, the sterilizing ratio was only 40.19%.

CONCLUSIONIt indicates that the sterilizing mechanism of EOW is mainly chemical processes (ACC), while the physical factors are auxiliary. The sterilizing mechanism of ERW is physics sterilizing that the mainly factor is ORP.

Electrolysis ; Sterilization ; methods ; Water ; chemistry

OBJECTIVETo investigate the ideal digestive tract reconstruction methods among three different surgical methods after radical gastrectomy of gastric cancer patients.

METHODSA total of 123 patients who received elective radical gastrectomy for gastric cancer from February 2010 to August 2011 were prospectively enrolled and randomly divided into radical proximal gastrectomy and jejunal interposition group, radical proximal gastrectomy and esophageal with the posterior of residual-stomach group, and radical total gastrectomy and Roux-en-Y esophagojejunostomy group. Patients were followed up for 12 months. Symptoms of reflux esophagitis were observed, gastric emptying tests were done, liver and kidney function was also monitored. The quality of life was documented before operation, and one and twelve months after operation.

RESULTSNo significant differences were found among these three groups in the pH value of lower part of esophagus, the blood regular test results and the functional parameters of kidney and liver before and after operation(all P>0.05). Symptoms of reflux esophagitis was reported in 1(2.4%) patients in the jejunal interposition group, 10(24.4%) in esophageal with the posterial of residual-stomach group, and 7(17.1%) in the Roux-en-Y esophagojejunostomy group(P=0.017). There was 1(2.4%), 10(17.1%), and 8(19.5%) patients presented reflux of barium meal in these three groups, respectively (P=0.046). There were no statistically significant difference in PH at the distal esophagus(6.9±0.2 vs. 6.8±0.1 vs. 6.9±0.1, P=0.196). The quality of life was significantly improved one year after surgery in terms of general status, physical function, emotional function, fatigue, nausea/vomiting, pain, constipation, and diarrhea (all P<0.05), with the jejunal interposition superior than the other two methods.

CONCLUSIONThree methods of digestive tract reconstruction in radical gastrectomy of gastric cancer patients can improve the health status and the quality of life in gastric cancer patients. Radical proximal gastrectomy and jejunal interposition is the preferred method.

Anastomosis, Roux-en-Y ; Anastomosis, Surgical ; Digestive System Surgical Procedures ; Esophagus ; Gastrectomy ; Gastric Emptying ; Gastric Stump ; Humans ; Jejunum ; Quality of Life ; Reconstructive Surgical Procedures ; methods ; Stomach Neoplasms ; surgery

OBJECTIVETo study effects of different intraabdominal pressure of carbon dioxide (Cq2) pneumoperitoneum on hemorrheology and microcirculation in rabbits.

METHODSEighteen female healthy rabbits weighing 2.2 kg to 3.5 kg were randomly divided into three groups equally based on pneumoperitoneum pressure: 0 mmHg group (group I),10 mmHg group (group II) and 15 mmHg (group III). Each group received 1 h pneumoperitoneum under different pressure. Blood samples were taken at 5 min before CO2 pneumoperitoneum, at 30 and 60 min after pneumoperitoneum for the measurements of indexes of hemorrheology. Hemodynamics including heart rate (HR), mean arterial pressure (MAP) and the volume and velocity of the microcirculation of auricle were continuously monitored, such indexes were recorded at the related time.

RESULTSAfer pneumoperitoneum at 30 and 60 min, compared with group I, HR, MAP, the whole blood viscosity, the aggregation and rigid indexes of RBC were significantly raised in group II (P < 0.05), the deformability indexes of RBC, the volume and velocity of the microcirculation were markedly decreased (P < 0.05). Even more significant changes were observed in group III (P < 0.01). The plasma viscosity and the hematocrit changed little.

CONCLUSIONAfter CO2 pneumoperitoneum, hemorrheology is decreased; Although HR, MAP are raised, the volume and velocity of the microcirculation are decreased.

Abdomen ; blood supply ; Animals ; Blood Viscosity ; Carbon Dioxide ; Female ; Hematocrit ; Hemorheology ; Microcirculation ; Pneumoperitoneum, Artificial ; methods ; Pressure ; Rabbits

AIDS-Related Opportunistic Infections ; diagnostic imaging ; drug therapy ; etiology ; Adult ; Bone Marrow Examination ; CD4 Lymphocyte Count ; Female ; Humans ; Male ; Middle Aged ; Mycoses ; diagnostic imaging ; drug therapy ; etiology ; Penicillium ; isolation & purification ; Prognosis ; Radiography

[Objective]To investigate the effect of GRACE scores on prediction of 30-day cardiovascular adverse events in acute chest pain patients.[Methods]A prospective,observational analysis was conducted in the patients with acute chest pain in Emergency Department(ED)from January 1,2016 through April 1,2016.Data including characteris-tics and GRACE scores were collected.All causes leading to MACE were followed up at 30th day after the onset of acute chest pain.[Results]Among a total of 209 patients presenting with acute chest pain enrolled in this study,110 were male (52.63%)and 99 were female(47.37%).The range of age was 20-98years old,and mean age was(65.28±16.85)years old.During follow-up period,12 patients had MACE,2 patients died in ED,3 patients died in hospital,6 patients died out of hospital,and 1 person was diagnosed with myocardial infarction. When compared with non-MACE group,factors including age,BMI,hospitalized patient number,and number of patients admitted in CCU as well as GRACE scores, were significantly higher in MACE group(P<0.05). The predictive ROC curve area of GRACE scores in 30-day MACE was 0.819(0.735 to 0.902). The optimal sensitivity and specificity were 0.92 and 0.65,respectively. The probability of 30-day cardiovascular adverse events in various GRACE score risk stratification was 0.95%(low-risk),6.67%(medi-um-risk),and 18.92%(high-risk),respectively.[Conclusion]The GRACE score was a useful predictor to the occur-rence of 30-day cardiovascular adverse events in acute chest pain patients.

BACKGROUNDWhether final kissing balloon (FKB) dilatation after one-stent implantation at left-main (LM) bifurcation site remains unclear. Therefore, this large sample and long-term follow-up study comparatively assessed the impact of FKB in patients with unprotected LM disease treated with one-stent strategy.

METHODSTotal 1528 consecutive patients underwent LM percutaneous coronary intervention in one center from January 2004 to December 2010 were enrolled; among them, 790 patients treated with one drug-eluting stent crossover LM to left anterior descending (LAD) with FKB (n = 230) or no FKB (n = 560) were comparatively analyzed. Primary outcome was the rate of major adverse cardiovascular events, defined as a composite of death, myocardial infarction (MI) and target vessel revascularization (TVR).

RESULTSOverall, The prevalence of true bifurcation lesions, which included Medina classification (1,1,1), (1,0,1), or (0,1,1), was similar between-groups (non-FKB: 37.0% vs. FKB: 39.6%, P = 0.49). At mean 4 years follow-up, rates of major adverse cardiovascular events (non-FKB: 10.0% vs. FKB: 7.8%, P = 0.33), death, MI and TVR were not significantly different between-groups. In multivariate propensity-matched regression analysis, FKB was not an independent predictor of adverse outcomes.

CONCLUSIONSFor patients treated with one-stent crossover LM to LAD, clinical outcomes appear similar between FKB and non-FKB strategy.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome

BACKGROUND:A new-type nano-bionic anti-adhesion hernia mesh was developed in our previous research.OBJECTIVE:To investigate the mechanical properties and cytocompatibility of the new-type nano-bionic anti-adhesion hernia mesh.METHODS:The tensile strength of the compound hernia mesh was detected using a textile detector.Mouse fibroblasts (L929) were cultured with the compound hernia mesh,and cell structures on the mesh surface were observed under electron microscope at 1,3,5 days after culture.In addition,L929 cells were co-cultured with compound hernia mesh,polypropylene patch,and polyester patch,respectively.Cells cultured alone were used as negative controls.After 1,3,5 days of culture,MTS array was used to detect cell proliferation and evaluate cytotoxicity;after 3 days of culture,western blot was used to detect the content of type Ⅰ and Ⅲ collagens.RESULTS AND CONCLUSION:The average tensile strength of the compound hernia mesh was 31.2 N The number of fibroblasts on the nanofibrous layer of the compound hernia mesh increased as long as cultured.The cells spread along the nanofibers and pseudopodia extended from the cells formed polygon and fusiform structures,with a good cross-linking with the mesh.A complete cell layer covered all pores of the nanofibers at 5 days.The cytotoxicity of the nanofibrous layer of the compound hernia mesh was graded 0,and the cytotoxicity was graded 1 of polypropylene and polyester patches.All the three kinds of patches fulfilled the implantation requirements,and the compound hernia mesh had better biological properties.No significant differences were found among groups in the contents of type Ⅰ and Ⅲ collagens at 3 days of culture.To conclude,the new-type nano-bionic anti-adhesion hernia mesh has good mechanical properties and cytocompatibility.