As the main active compound of Stephania tetrandra S. Moore, tetrandrine (TET) has been used to treat silicosis for nearly 50 years. TET has clear therapeutic effect on pulmonary fibrosis and lung cancer. A recent study suggests that TET may inhibit the replication of SARS-CoV-2 by blocking the two-pore channel 2 (TPC2), revealing its potential as a natural medicine to treat COVID-19. To explore the material basis of TET targeting lung efficacy and its potential toxicity, available literatures related to the pharmacological activity on pulmonary, dosage, toxicity and pharmacokinetics of TET are systemically reviewed. The prospect and current problems of TET to be a therapeutic agent for COVID-19 are further investigated on this basis.

To reduce the problems of poor solubility, high in vivo dosage requirement, and weak targeting ability of paclitaxel (PTX), a hyaluronic acid-octadecylamine (HA-ODA)-modified nano-structured lipid carrier (HA-NLC) was constructed. HA-ODA conjugates were synthesized by an amide reaction between HA and ODA. The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC. The HA-NLC displayed strong internalization in cluster determinant 44 (CD44) highly expressed MCF-7 cells, and endocytosis mediated by the CD44 receptor was involved. The HA-NLC had an encapsulation efficiency of PTX of 72.0%. The cytotoxicity of the PTX-loaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol®. In vivo, the HA-NLC exhibited strong tumor targeting ability. The distribution of the NLCs to the liver and spleen was reduced after HA modification, while more nanoparticles were aggregated to the tumor site. Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.

OBJECTIVE: To investigate the effects of corneal thickness distribution and apex position on postoperative refractive status after full-bed deep anterior lamellar keratoplasty (FBDALK). METHODS: This is a retrospective analysis of patients who were diagnosed with advanced keratoconus between 2011 and 2014 in our hospital. The base of the cone in all patients did not exceed the central cornea at a 6-mm range. The FBDALK was performed by a same surgeon. All patients had a complete corneal suture removal and the follow-up records were intact. Patients who had graft-bed misalignment or who were complicated with a cataract or glaucoma were excluded. Uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), and Pentacam examination data were recorded at two years postoperatively. The recorded data included the superior-inferior (S-I) and nasal-temporal (N-T) corneal thickness differences in 2, 4, 6, and 8 mm diameter concentric circles with the corneal apex as the center (S-I_{2 mm}, S-I_{4 mm}, S-I_{6 mm}, S-I_{8 mm}, N-T_{2 mm}, N-T_{4 mm}, N-T_{6 mm}, and N-T_{8 mm}), the linear, X-axis, and Y-axis distance between the corneal pupillary center and the cornea apex, total corneal astigmatism at a zone of 3 mm diameter from the corneal apex (TA_{3 mm}), the astigmatic vector values J₀ and J₄₅, and the corneal total higher-order aberration for 3 and 6 mm pupil diameters (HOA_{3 mm} and HOA_{6 mm}). Statistical analysis was performed by SPSS 15.0. RESULTS: A total of 47 eyes of 46 patients met the criteria and were included in this study. The mean follow-up time was (28±7) months. The mean UCVA was 0.45±0.23 (logMAR) (MAR: minimum angle of resolution) and the mean BSCVA was 0.19±0.15 (logMAR), which were all significantly positively correlated with postoperative TA_{3 mm} and HOA_{3 mm}. The mean S-I corneal thickness differences were (44.62±37.74) μm, and the mean N-T was (38.57±32.29) μm. S-I_{2 mm} was significantly positively correlated with J₀ (r=0.31), J₄₅ (r=0.42), HOA_{3 mm} (r=0.37), and HOA_{6 mm} (r=0.48). S-I_{4 mm} and S-I_{8 mm} were significantly positively correlated with HOA_{3 mm} (r=0.30, r=0.40) and HOA_{6 mm} (r=0.46, r=0.35). The X-axis distance between corneal pupillary center and corneal apex was significantly positively correlated with J₄₅ (r=0.29). CONCLUSIONS In patients with advanced keratoconus after FBDALK, the unevenly distributed thickness at corneal pupillary area and the misalignment of corneal apex and pupillary center might cause significant regular and irregular astigmatism, which affected the postoperative visual quality.
Adolescent ; Adult ; Cornea/surgery* ; Corneal Transplantation/methods* ; Cryopreservation ; Female ; Follow-Up Studies ; Humans ; Keratoconus/diagnosis* ; Keratoplasty, Penetrating/methods* ; Male ; Retrospective Studies ; Visual Acuity ; Young Adult

As the dilution procedure was applied, a simple, rapid and cost-effective high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of aflatoxin B1, B2, G1, and G2 was successfully by performed in a total 83 samples of 10 traditional Chinese medicines (TCMs), which were collected from 5 different hospital pharmacies and 5 different medical stores in Guangzhou city. Matrix effects of these 10 TCMs were ranged from 80.23% to 115.5% in low, intermediate and high concentration levels, indicating that the negative effect was overcome in this study. Meanwhile, the analysis method was proved to be stable and reliable during the whole analysis using Semen Armeniacae Amarum spiked 3 concentration levels of standard solution as quality control samples and the RSD < 6.6% was obtained. The contamination levels of 83 investigated samples were 13.89% and 17.02% in hospital pharmacies and medical stores, respectively. The result was presented to provide relevant reference and supplement to those researchers in TCMs analysis and screening.
Aflatoxin B1 ; analysis ; Aflatoxins ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drug Contamination ; Medicine, Chinese Traditional ; Quality Control ; Tandem Mass Spectrometry ; methods

OBJECTIVETo construct a recombinant adenovirus vector containing bone morphogenic protein-7 (BMP-7) gene and to identify its biological activities in proximal tubule epithelial cells (PTECs).

METHODSForty-six fragments of BMP-7 gene were obtained by PCR method and then were ligated to the full-length gene. The full length sequence of BMP-7 was subcloned into pBluescript II(+) vectors, and confirmed by sequencing. Double digested with Not I and Hind III, BMP-7 gene was inserted into pShuttle-CMV. EcoR I pre-linearized pShuttle plasmid was transformed into competence bacterium BJ5183 to obtain the recombinant adenovirus-BMP-7 by efficient homologous recombination. Then the AdBMP-7 was obtained by packaging Pac I linearized in 293 cells. Adenoviral titer was determined by adenovirus fluorescent detection kit. The protein expression of BMP-7 in PTECs was respectively detected by ELISA and Western blot. RT-PCR method was used for analyzing the alpha-smooth muscle action (alpha-SMA) expression in PTECs, which was treated consecutively with TGF-beta and AdBMP-7.

RESULTSThe recombinant plasmid AdBMP-7 was successfully generated, which increased BMP-7 protein expression levels in PTECs, and down-regulated TGF-beta-induced alpha-SMA expression.

CONCLUSIONThe bioactive recombinant adenovirus AdBMP-7 has been successfully constructed, which may be effective in inhibition of chronic renal fibrosis.

Adenoviridae ; genetics ; metabolism ; Animals ; Base Sequence ; Bone Morphogenetic Protein 7 ; biosynthesis ; genetics ; Cells, Cultured ; Epithelial Cells ; metabolism ; Genetic Vectors ; genetics ; Kidney Tubules, Proximal ; cytology ; metabolism ; Molecular Sequence Data ; Rats ; Recombinant Proteins ; biosynthesis ; genetics

OBJECTIVETo study the influence of various glucose levels on the structure and function of cultured neonatal rats cardiomyocytes.

METHODCultured neonatal ventricular cardiomyocytes were treated with various glucose levels for 5 days: control (5.5 mmol/L); high (25.5 mmol/L); intermittent high (5.5 mmol/L or 25.5 mmol/L in every 12 hours interval); high (25.5 mmol/L) + PKC inhibitor Ro-31-8220 (50 nmol/L). Then, the cell beating frequency was counted, the cardiomyocytes diameters were measured and the expressions of PKC-alpha, PKC-beta(2), p-PKC-alpha, p-PKC-beta(2), NF-kappaB and c-fos were determined by Western blot.

RESULTSCompared with control group, cardiomyocytes beating frequency, diameters as well as the expressions of PKC-alpha, PKC-beta(2), p-PKC-alpha, p-PKC-beta(2), NF-kappaB and c-fos were significantly increased in high glucose concentration (all P < 0.05) and intermittent high glucose treatment further amplified these changes (all P < 0.05 vs. high glucose and control groups). High glucose induced changes could be significantly attenuated with PKC inhibitor Ro-31-8220.

CONCLUSIONHigh, especially intermittent high glucose could lead to diabetic cardiomyopathy by promoting cardiac hypertrophy, increasing beating frequency via activating PKC/NF-kappaB/c-fos pathways.

Animals ; Cells, Cultured ; Glucose ; metabolism ; Myocytes, Cardiac ; cytology ; metabolism ; NF-kappa B ; metabolism ; Protein Kinase C ; metabolism ; Rats ; Rats, Sprague-Dawley

Adolescent ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic ; pathology ; Neutrophils ; pathology ; Skin Neoplasms ; pathology

Objective To establish an acute yunaconitine poisoning rat model with a single oral administration and to determine the contents of yunaconitine in rat tissues by UPLC-MS/MS method, then investigate the distribution of yunaconitine in rats. Method The rats were randomly divided into three groups and were intragastrically administered a single dose of 2.2mg/kg,1.1mg/kg,0.7mg/kg yunaconitine, respectively.. The rats were killed 2h later, the stomach tissue, intestine tissue, liver tissue, pancreas tissue, kidney tissue, lung tissue, spleen tissue, heart tissue, bladder tissue, testis tissue, brain tissue and heart blood samples were collected. The contents of yunaconitine in the biological materials were determined by UPLC-MS/MS method after the biological samples extracted by liquid-liquid extraction. Result A rat model of the yunaconitine poisoning was made with a single dose of 1.1mg/kg, the concentrations of yunaconitine displayed in the organs with the following order:stomach, small intestine, liver, pancreas, kidney, lung, spleen, heart, bladder, testis, heart blood and brain. Conclusion Yunaconitine was widely distributed in rats, especially the levels in the stomach, small intestine and liver were the highest. The conclusion provides a basis for the selection of test materials for the poisoning of Aconitum vilmorinianum Kom.

Objective To evaluate risk factors for central venous catheter-related bloodstream infection(CRBSI)in intensive care unit(ICU)patients by Meta analysis. Methods Literatures about risk factors of CRBSI in ICU pa-tients were retrieved from databases of Cochrane Library,PubMed,Embase,CBM,CNKI,and WanFang Data,RevMan 5.3 software was used for Meta analysis.Results There are 12 literatures in accordance with the inclusion criteria,with a total sample size of 14 422 cases,5 cohort studies and 7 case-control studies,the Newcastle-Ottawa Scale(NOS)scores were 4-6 points. According to Meta analysis,duration of indwelling catheter(WMD,12.25 [95%CI,5.55-18.94]),multi-cavity catheter(OR,3.52[95% CI,1.46-8.52]),femoral vein catheterization (OR,2.44[95%CI,1.34-4.46]),parenteral nutrition(O R,2.47[95% CI,1.18-5.21]),length of stay in ICU(WMD,10.01[95%CI,4.17-15.85]),APACHE II score(WMD,4.46[95%CI,1.25-7.66]),and dia-betes mellitus(OR,1.83[95% CI,1.08-3.09])were significantly different in each group(all P<0.05). Conclusion Risk factors for CRBSI in ICU patients are duration of indwelling catheter,multi-cavity catheter,femo-ral vein catheterization,parenteral nutrition,length of stay in ICU,APACHE II score,and diabetes mellitus. However,due to the limitation of methodological quality of included studies,more strictly designed and large sam-ple prospective studies are needed to verify the result.

Objective To investigate the different characteristics of apoptosis during the different phases of cell cycle between astrocytes and neurons, so as to explore the apoptosis mechanism of the 2 kinds of cells. Methods Ischemia/reperfusion injury was induced by temporary middle cerebral artery occlusion (MCAO). And the brain was taken 3 d after injury. Thymidine analogues such as bromodeoxyuridine (BrdU) was used to incorporate during the S phase of the cell cycle, and the combined visualization of BrdU labeling and Tdt-mediated dUTP-biotin nick end labeling was performed to investigate the apoptosis in the adult rat brain in vivo. Then the apoptosis during the different phases of cell cycle between astrocytes and neurons was detected by flow cytometry (FCM) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods. Results Compared to the normal controls, BrdU or TUNEL positive cells were increased in injury group, and a few of of BrdU and TUNEL double positive cells were found. The most apoptotic neurons and astrocytes were in G0/G1 phase, and the apoptotic neurons were less than astrocytes in G0/G1 phase (P＜0.01), but the apoptotic neurons were more than astrocytes in S phase (P＜0.01). Conclusions Astrocytes and neurons may have the different characteristics of apoptosis during the different phases of cell cycle, which is induced at different check-points.