Analysis of animal models of stable chronic obstructive pulmonary disease based on clinical features of traditional Chinese medicine and western medicine / 中国中药杂志

This study analyzed the advantages and disadvantages of existing animal models in China and abroad and their goodness of fit based on the clinical characteristics and diagnostic criteria of stable chronic obstructive pulmonary disease(COPD) in traditional Chinese medicine(TCM) and western medicine, followed by the collation and summarization of model evaluation methodologies. The results showed that the existing animal models of stable COPD were mainly modeled via smoke exposure or the combination of multiple methods like smoke exposure plus lipopolysaccharide or protease or bacterial infection. These animal models generally failed to simulate the clinical characteristics of TCM, and their goodness of fit in western medicine was higher than that in TCM. There is a lack of research on the animal models of stable COPD and the disease-syndrome combination models. Although the modeling is guided by the pathogenesis or mechanism of diseased humans, the established models were still not identical with the actual clinical situations. In-depth research is needed to develop quantitative standards for stable COPD models.

Clinical Efficacy of Endoscopic Tympanoplasty for Large Tympanic Membrane Perforation / 中山大学学报(医学科学版)

@#【Objective】To investigate the clinical efficacy of endoscopic tympanoplasty for chronic suppurative otitis with large tympanic membrane perforation.【Methods】A total of 110 cases（115 ears）which were diagnosed as chronic suppurative otitis with large tympanic membrane perforation were retrospectively collected from May 2017 to Jan 2019. All cases were performed endoscopic tympanoplasty；including removing tympanic lesions，reconstruction of ossicular chain， and myringoplasty with cartilage and perichondrium complex by underlay technique. At the same time of tympanoplasty ， balloon eustachian tuboplasty（BET）was performed in patients who were diagnosed with eustachian tube dysfunction. The graft success rate，pure tone threshold average（PTA）of speech frequency and the air-bone gap（ABG）were assessed at 3 months after surgery.【Results】The primary graft success rate was 95.7%，and the PTA and ABG were（25.7±11.8）dB HL and（13.8 ± 6.9）dB HL，respectively，which showed significant differences compared with pre- operation conditions （P < 0.001）. Furthermore，29 ears which were diagnosed with eustachian tube dysfunction were treated with BET at the same time of tympanoplasty. Compared with simply tympanoplasty （86 ears），no difference was found in primary graft success rate ，PTA and ABG post-operation（P > 0.05）.【Conclusions】 Endoscopic tympanoplasty is an effective surgery，and the cartilage and perichondrium complex is a reliable repair material for large tympanic membrane perforation ，which are both worthy of clinical promotion. Furthermore ，BET at the same time of tympanoplasty could ensure clinical efficacy for the patients with eustachian tube dysfunction.

Effect of Bifidobacterium on the expression of β-defensin-2 in intestinal tissue of neonatal rats with necrotizing enterocolitis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effect of Bifidobacterium on the expression of β-defensin-2 (BD-2) in intestinal tissue of neonatal rats with necrotizing enterocolitis (NEC).</p><p><b>METHODS</b>A total of 40 rats were randomly divided into four groups: normal control, Bifidobacterium control, NEC model, and Bifidobacterium treatment, with 10 rats in each group. A rat model of NEC was induced by hypoxia, cold stimulation, and artificial feeding. The rats in the Bifidobacterium control and Bifidobacterium treatment groups were given Bifidobacterium via the gastric tube after cold stimulation once a day for three consecutive days. The morphological changes of the terminal ileum were observed under a light microscope and the intestinal injury score was determined. Immunohistochemistry and qRT-PCR were used to measure the protein and mRNA expression of BD-2 in the ileal mucosal tissue.</p><p><b>RESULTS</b>The NEC model group had a significantly higher intestinal injury score than the normal control, Bifidobacterium control, and Bifidobacterium treatment groups (P<0.05). The Bifidobacterium treatment group had a significantly higher intestinal injury score than the normal control and Bifidobacterium control groups (P<0.05). The mRNA and protein expression of BD-2 in the normal control group was significantly lower than in the Bifidobacterium control, NEC model, and Bifidobacterium treatment groups (P<0.05). The Bifidobacterium control group had significantly higher mRNA and protein expression of BD-2 than the NEC model and Bifidobacterium treatment groups (P<0.05). The Bifidobacterium treatment group had significantly higher mRNA and protein expression of BD-2 than the NEC model group (P<0.05).</p><p><b>CONCLUSIONS</b>Bifidobacterium can induce the expression of BD-2 in intestinal tissue of rats and reduce inflammatory response by increasing the expression of BD-2. This provides a protective effect on neonatal rats with NEC.</p>

Repeated injection of mitoxantrone containing thermosensitive liposomes in rat induced ABC phenomenon / 药学学报

To investigate whether accelerated blood clearance (ABC) phenomenon could be induced after repeated injection of mitoxantrone thermosensitive liposomes, LC-MS/MS and enzyme linked immunosorbent assay (ELISA) were used to measure the concentration of mitoxantrone and the anti-polyethylene glycol (PEG) IgM levels in rat plasma, separately. The drug was rapidly cleared away after the second administration. The anti-PEG IgM was detected after the first dose which was neutralized quickly after the second dose. It is proved that repeated administration of mitoxantrone thermosensitive liposomes in rat caused the ABC phenomenon.

Novel cationic liposome loading siRNA inhibits the expression of hepatitis B virus HBx gene / 药学学报

In order to solve the problem of selection and in vivo delivery problem in siRNA treatment, hepatitis B virus (HBV) HBx gene which could be targeted by siRNA was studied. The siRNA expression plasmid which specific inhibits HBx expression was obtained by in vitro selection via a dual-luciferase plasmid including HBx-Fluc fusion protein expression domain. The selected siRNA expression plasmid was then encapsulated in PEG-modified cationic liposome, which was devoted into pharmacodynamic studies at both cellular and animal level. The results illustrated that the cationic liposome which encapsulated siRNA expression plasmid could effectively inhibit HBx gene expression both in vitro and in vivo.

Assessment of left ventricular function in patients with aortic regurgitation using tow-dimensional speckle-tracking echocardiography / 中华医学超声杂志（电子版）

Objective Analyse the change of left ventricular (LV) longitudinal and radial strain in patients with aortic regurgitation (AR) and discuss the relationship between the 2D strain parameter and the filling and ejection of LV. Methods Thirty healthy controls and 45 patients with AR (24 patients with moderate AR and 21 with severe AR) were enrolled in this study, LV systolic global peak radial strain(GRS), systolic global peak longitudinal strain(GLS) and systolic peak longitudinal strain(S), systolic peak longitudinal strain rate(SRs), early diastolic peak longitudinal strain rate(SRe) of every segment were measured or calculated using 2D-STE, early and late diastolic transmitral flow velocity (E, A) were recorded by pulsed Doppler echocardiography and early diastolic mitral annular velocity (Ea) were assessed by tissue Doppler imaging,the E/A and E/Ea ratio were calculated. Discuss the relationship of GLS and LV ejection fraction (LVEF), GLS and E/Ea using the Pearson correlation analysis. Results The GLS were (-20.09±1.47)%, (-18.68±1.52)%, (-12.56±3.25)%and the GRS were (46.71±7.65)%, (43.01±5.95)%, (28.52±6.13)% in control group, patients with moderate and severe AR (MAR group and SAR group) respectively. There were significant differences among the groups (F =82.08,47.69, both P < 0.01) as following:SAR group with control group and MAR group [ q=17.56,13.60 (GLS), q=13.44, 10.20 (GRS), all P<0.01),MAR group and control group [ q=3.42 (GLS), P<0.01]. The SRs of the apical segment were (-1.24±0.22)s-1, (-1.19±0.25)s-1, (-1.04±0.28)s-1 in control group,MAR group and SAR group respectively. There were significant differences among the groups (F=4.47, P < 0.05) as following:SAR group with control group and MAR group ( q=4.02,3.28, both P<0.01). The S, SRe of apical segment and the S,SRs,SRe of basal and midventricular in MAR group were all lower than the control group ( q=4.42, 5.01, 3.48, 3.24, 4.78, 4.12, 3.61, 6.72, all P < 0.01). Pearson correlation analysis revealed the GLS had a relationship with LVEF and E/Ea ( r=-0.73, 0.64, both P<0.01). Conclusion The reduced longitudinal strain and strain rate could detect LV dysfunction in patients with AR in early stage and the GLS had the ability to reflect the diastolic filling and systolic ejecting of the LV.

Relationship between pulmonary surfactant-associated protein B polymorphisms and the susceptibility to neonatal respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the relationship between pulmonary surfactant-associated protein B (SP-B) gene polymorphisms and their susceptibility to neonatal respiratory distress syndrome (RDS).</p><p><b>METHODS</b>Eighty-eight preterm infants with RDS (RDS group) and 103 infants without RDS (control group) were enrolled. The genomic DNA was isolated using DNA kits. Polymerase chain reaction with restriction fragment length polymorphism technique was used to detect the genotype and allele frequency of the SP-B -18A/C and SP-B 1580C/T single nucleotide polymorphisms. The association between the polymorphisms and RDS was analyzed.</p><p><b>RESULTS</b>SP-B -18A/C and SP-B 1580C/T were found to be polymorphic in both RDS and control groups. The frequencies of CC genotype (X2=12.26, P<0.01) and C allele (X2=11.97, P<0.01) of SP-B 1580C/T were significantly higher in the RDS group than in the control group. The C allele significantly increased the risk of RDS (OR=2.26, 95%CI: 1.42-3.60). The frequencies of genotype and allele of SP-B -18A/C showed no significant difference between the two groups.</p><p><b>CONCLUSIONS</b>SP-B 1580C/T polymorphism contributes to the etiology of RDS and may serve as the susceptibility gene for RDS. The C allele increases the risk of RDS. SP-B -18A/C shows no association with the etiology of RDS.</p>

The value of myocardial contrast echocardiography combined with dobutamine stress echocardiography in early diagnosis of coronary artery disease / 中华医学超声杂志（电子版）

Objective To investigate the value of myocardial contrast echocardiography(MCE)combined with high-dose dobutamine stress echocardiography(DSE)in the early diagnosis of coronary artery disease(CAD).Methods The dobutamine stress MCE and SonoVue contrast infusion were performed before an elective percutaneous coronary intervention in 38 patients with suspected CAD.The total and regional perfusion were scored as normal or abnormal and attributed to the three main epicardial coronary arteries using a 16-segment left ventricular model.Results An intermediate stress level was obtained in 22(58%)patients,and 9(24%)patients were obtained with peak stress.Twenty seven of 38 patients were diagnosed as CAD by quantitative coronary angiography.A perfusion defect was detected in 89% of the patients at peak stress,compared to 37% at baseline,there was significant difference(χ2=15.565,P<0.01).ConclusionsThe MCE combined with DSE can increase the sensitivity of myocardial ischemia detection.As a new non-invasive method,MCE combined with DSE could be used in the early diagnosis of CAD.

Study on total glucosides of peony preventing non-obese diabetic mice from sialoadenitis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the immunosuppressive effect of total glucosides of peony (TGP) on sialoadenitis in non-obese diabetic mice (NOD mice) and explore its possible mechanism.</p><p><b>METHODS</b>27 female five-week-old NOD mice were randomly divided into three groups: TGP, hydroxychloroquine (HCQ) and normal saline (NS) group. One week later, they were administered intragastrically in TGP, HCQ and NS respectively. Three mice from each group were sacrificed at the age of 10, 15 and 20 weeks. The saliva flow, serum and submandibular glands were collected at these time points. Histological changes of submandibular glands were examined by HE staining. The expression of autoantibodies (SSA, SSB and anti-alpha-fodrin) and associated cytokines in serum were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Compared with the NS group, salivary flow was significantly increased, the extent of the histological changes were ameliorated, the autoantibodies in serum were significantly decreased and the imbalance of Th1/Th2 cytokines was remedied in the mice treated with TGP and HCQ. There were no significant differences between the two groups treated with TGP and HCQ (P > 0.05).</p><p><b>CONCLUSION</b>TGP can effectively ameliorate sialoadenitis on NOD mice. The mechanism was thought to be associated with the protection of submandibular gland from intense inflammation and the correction of Th1/Th2 cytokines imbalance.</p>

Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride / 药学学报

This study is to compare the pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone (Mit-lipo) and free mitoxantrone (Mit-free). The antineoplastic effect of Mit-lipo was evaluated on PC-3 human xenograft tumor model after repeated intravenous injection at dose levels of 1, 2 and 4 mg x kg(-1). The pharmacokinetic study of Mit-lipo and Mit-free was performed on dogs following a single intravenous injection. The tissue distribution of Mit-lipo and Mit-free was observed on S-180 bearing mice after a single intravenous injection. (1) Pharmacodynamics: Mit-lipo dose-dependently inhibited PC-3 tumor growth at a dose ranging from 1 to 4 mg x kg(-1). The antitumor effect studies showed that Mit-lipo significantly improved the therapeutic effect in comparison with free drug. (2) Pharmacokinetics: in comparison with Mit-free, the AUC and t(1/2) values of Mit-lipo at the same dose level were higher than those of Mit-free in Beagle dogs. The results showed that Mit-lipo had long circulation characteristics. (3) Tissue distribution in S-180 bearing mice: compared to Mit-free, Mit-lipo preferentially accumulated into tumor zones instead of normal tissues. Tumor AUC in Mit-lipo treated animals was 8.7 fold higher than that in mice treated with the same dose of Mit-free. The Cmax values of Mit-lipo in heart, kidney, lung, spleen and intestinal tissue in Mit-lipo were 30.2%, 161.6%, 20.2%, 27.9% and 78.3% lower than those of Mit-free, respectively. The pharmacokinetics and tissue distribution of Mit-lipo changed obviously, thus increasing therapeutic effect and improving drug therapeutic index.

Study on the transmission of Hantaan virus and Orientia tsutsugamushi by naturally dual infected Leptotrombidium scutellare through stinging / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate whether Leptotrombidium scutellare could be naturally infected by both Hantaan virus (HV) and Orientia tsutsugamushi (OT) and transmission status by stinging.</p><p><b>METHODS</b>3459 Leptotrombidium scutellares from mice bodies and 3265 which were free were collected in the epidemic area of hemorrhagic fever with renal syndrome (HFRS) and tsutsugamushi disease.15 days later, the suspensions of lung and spleen of mice with 6 in a group stung by 1, 5 or 10 infected mites were injected intra-cerebrally into other mice for the detection of HV and OT in the next 6 generations of the mice, with immunofluorescent antibody technique (IFAT) and Giemsa staining technique. The passages of Vero-E6 cells inoculated on the aseptic filtrations from different number of infected mites were used to detect HV and OT pathogens. HV-RNA and OT-DNA were detected by PCR.</p><p><b>RESULTS</b>After passage, HV positive mouse body mite group out of both 5 and 10 mites in the sixth generation, OT positive mouse body mite group out of the 10 mites in the sixth generation, both HV and OT positive mouse body mite group out of 1 mite in the fifth and sixth generation, both HV and OT positive mouse body mite group out of 5 and 10 mites in the sixth generation, and free mites group out of 1, 5 and 10 mites in the sixth generation, were found one mouse infected by both HV and OT, respectively. Out of the fourth generation of Vero-E6 cells, one sample was found both HV and OT positive out of 5 and 10 HV and OT mouse body mite group, respectively. In the sixth generation, both HV and OT positive cells were detected in one mouse mite group and the 1, 5, 10 free mite groups, respectively. HV-RNA and OT-DNA were all detected by PCR.</p><p><b>CONCLUSION</b>Both HV and OT could be coexisted in wild Leptotrombidium scutellare and transmitted by stinging.</p>

Study on the mechanism of reversing multidrug resistance of hepatocarcinoma by bromocriptine / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of reversing multidrug resistance of hepatocarcinoma by bromocriptine (BCT) in vitro and in vivo.</p><p><b>METHODS</b>Three groups of cultured HepG2 cells were used: HepG2 (group A), the multidrug resistance HepG2/ADM cells (group B), and the HepG2/ADM cells treated with BCT (group C). Rhodamine 123 test was used to detect the function of P-gp protein. MTT assay was performed to examine the IC50. Multidrug resistance index to common five anticancer drugs of different concentrations of BCT and immunocytochemistry was performed to detect the expression of PKC-a protein. P-gp protein levels of the cells of each group were determined by Western blot. In addition, HepG2 and HepG2/ADM were injected into the livers of the nude mice (NM) (named NM HepG2, NM ADM, NM BCT groups respectively). The BCT group mice were treated with bromocriptine through gastric feedings. The sizes of the tumor growths in the livers were measured using B ultrasound. The MDR1mRNA levels in these tumor tissues were determined by reverse transcription polymerase chain reaction (RT-PCR) and the apoptosis rates of them were measured with TUNEL assay. 99mTc-MIBI SPECT was performed to detect the tumor 99mTc-MIBI accumulation index before and after the BCT treatment.</p><p><b>RESULTS</b>The rate of reversing resistance to ADM by BCT was 45.68% shown by using MTT assay, and the intracellular Rho123 accumulation increased more than two times compared with the control group shown by flow cytometric assay at the concentration of 10 micromol/L BCT and the effect was time-dependent. Between group B and group C there was a significant difference in the expression of PKC-alpha protein by immunocytochemistry detection (q = 5.37, P < 0.01), but there was no significant difference in the expression of P-gp protein between the two groups (q = 1.86, P > 0.05) . There was no notable difference of growth rates of the transplanted liver tumors among the three NM groups (F = 6.39, P > 0.05), and the inhibition rate of tumor volume and weight in NM BCT was higher than that in NM ADM (q1 = 5.89, q2 = 4.92, P < 0.01), but similar to that in NM HepG2 (q1 = 2.47, q2 = 3.02, P > 0.05). No difference was detected in MDR1mRNA between NM ADM and NM BCT using RT-PCR (q = 3.71, P > 0.05). The average number of apoptotic cells per high-power field (25.7+/-1.8) in NM BCT tumor tissues was higher than that in group ADM (2.7+/-0.2) (q = 3.72, P < 0.01), but similar to that of NM HepG2 (23.9+/-1.6) (q = 1.43, P > 0.05). The uptake of 99mTc-MIBI in all the NM after BCT therapy was significantly higher than that before the BCT treatment (t = 3.58, P < 0.01).</p><p><b>CONCLUSIONS</b>BCT can reverse multidrug resistance of hepatocarcinomas by inhibiting the function of P-gp protein and can enhance the susceptibility of HepG2/ADM cells to cytotoxic drugs.</p>

Synergistic effect of bromocriptine combining tumor necrosis factor-alpha on reversing multidrug resistance in a nude mouse model of liver neoplasm / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate synergistic effect of bromocriptine (BCT) combining tumor necrosis factor-alpha (TNF-alpha) on reversing multidrug resistance in a nude mouse model of liver neoplasm.</p><p><b>METHODS</b>Human hepatocarcinoma cell line HepG(2) (HepG(2) group), drug resistant hepatocarcinoma cell line HepG(2)/adriamycin (HepG(2)/ADM group) and hepatocarcinoma cell line transfected with TNF-alpha gene HepG(2)/ADM/TNF (TNF group and BCT group) were injected into the liver of nude mice via orthotopic implantation to establish multidrug resistance model of liver neoplasm in vivo. All the mice were injected with 5-fluouracil + adriamycin + mitomycin in abdominal cavity for 7 d. The mice in BCT group was simultaneously given bromocriptine through gastric canal. Size and weight of the tumor were measured. Furthermore tumor histological character and growth of the nude mice was observed and its chemosensitivity was tested. MDR associated genes and proteins (MRP, LRP) of implanted tumors were detected by immunohistochemical staining and reverse transcriptive polymerase chain reaction (RT-PCR), and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay.</p><p><b>RESULTS</b>The nude mouse model of each cell line was all inoculated successfully. The tumor growth rate and weight were significantly different among groups (P < 0.05). After chemotherapy tumor growth inhibition rate was higher in BCT group (67%) compared to ADM and TNF groups (P < 0.01), and similar to HepG(2) group (54%). MDR1 and LRP mRNA could be detected in all groups, but TNF-alpha was detected only in TNF-alpha and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF-alpha and BCT groups was low similar to HepG(2) group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups (P < 0.05) with TUNEL assay.</p><p><b>CONCLUSIONS</b>TNF-alpha gene can down-regulate the MDR associated genes and proteins expression for example MDR1, LRP, and lower its tumorgenesis. Moreover, bromocriptine can enhance the susceptibility of HepG(2)/ADM cells to cytotoxic drugs.</p>