Chinese Herbal Medicine Feiyanning Prescription Regulates EMT to Reverse Cisplatin Resistance in Non-small Cell Lung Cancer / 中国实验方剂学杂志

ObjectiveTo observe the effect of Feiyanning prescription （FYN） on cisplatin （DDP） resistance in non-small cell lung cancer （NSCLC） and explore the underlying mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the proliferation of A549 and A549/DDP （DDP-resistant） cells treated by DDP （0， 2.0， 4.0， 6.0， 8.0， 10.0 mg⋅L-1） and the proliferation of A549/DDP cells treated by FYN （0， 100， 200， 300， 400， 500， 600 mg⋅L-1）. Based on immunofluorescence staining and Western blot （WB）， the expression of epithelial mesenchymal transition （EMT）-related proteins in A549 and A549/DDP groups was observed. A549/DDP cells were classified into control group， FYN group （200 mg⋅L-1）， DDP group （6.0 mg⋅L-1）， and combination group ［FYN （200 mg⋅L-1） + DDP （6.0 mg⋅L-1）］ and respectively treated with corresponding drugs. Then， invasion ability of each group was examined by transwell assay， and the expression of EMT-related proteins in each group by WB. Moreover， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and immunofluorescence staining were separately applied to detect the mRNA and protein expression of drug resistance-related factors in each group， respectively. ResultCompared with A549 group， A549/DDP group showed high resistance to DDP （P<0.01）， low expression of E-cadherin， and high protein expression of Vimentin， N-cadherin， and Snail （P<0.05， P<0.01）. As compared with the control group， FYN inhibited the proliferation of A549/DDP cells in a concentration-dependent manner （P<0.01）， and the FYN group， DDP group， and combination group demonstrated low invasion ability （P<0.01）. In addition， the invasion ability in the combination group was particularly lower than that in the DDP group （P<0.01）. The expression of E-cadherin protein was higher and the protein expression of N-cadherin， Vimentin， and Snail was lower in the in FYN group than in the control group （P<0.01）. The protein expression of E-cadherin， N-cadherin， and Vimentin was lower and the expression of Snail was higher in the DDP group than in the control group （P<0.05，P<0.01）. The protein expression of E-cadherin， N-cadherin， Vimentin， and Snail in the combination group decreased as compared with that in the control group （P<0.01）. Compared with the DDP alone， the combination raised the expression of E-cadherin and lowered the protein expression of N-cadherin， Vimentin， and Snail （P<0.01）. The protein and mRNA expression of lung resistance-related protein （LRP） and multidrug resistance 1 （MDR1） was lower and the protein and mRNA expression of topoisomerase Ⅱα （TOPO Ⅱα） was higher in the FYN group than in the control group （P<0.01）. The protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα was higher in the DDP group than in the control group （P<0.01）. The expression of LRP protein and mRNA showed no significant variation， but the protein and mRNA expression of MDR1 and TOPO Ⅱα increased in the combination group compared with those in the control group （P<0.01）. Compared with the DDP group， FYN group and combination group showed low protein and mRNA expression of LRP and MDR1 and high protein and mRNA expression of TOPO Ⅱα （P<0.01）. Compared with FYN， the combination elevated the protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα （P<0.01）. ConclusionFYN prescription can reverse the DDP resistance of NSCLC by modulating EMT.

Mutual information-based contrastive learning for the generation of pseudo-CT images of the head from magnetic resonance imaging / 中华放射医学与防护杂志

Objective:To compare the abilities of different neural networks to generate pseudo-computed tomography (CT) images from magnetic resonance imaging (MRI) images and to explore the feasibility of pseudo-CT for clinical radiotherapy planning.Methods:A total of 29 brain cancer patients with planning CT and diagnostic MRI were selected. 23 of these patients were used for training neural networks and 6 for testing pseudo-CT images. Cycle-consistent generative adversarial network (cycleGAN), contrastive learning for unpaired image-to-image translation (CUT), and improved network denseCUT proposed in this study were applied to generate pseudo-CT images from MRI images. The pseudo-CT images were imported into a clinical treatment planning system to verify the feasibility of applying this method to radiotherapy planning.Results:The comparison between the generated pseudo-CT images and real CT images showed that the mean absolute errors were (72.0±6.9), (72.5±8.0), and (64.6±7.3) HU for the cycleGAN, CUT, and denseCUT, respectively. Meanwhile, the structure similarity indices were 0.91±0.01, 0.91±0.01, and 0.93±0.01, respectively. The peak signal-to-noise ratios were (28.5±0.7), (28.5±0.7), and (29.5±0.7) dB, respectively. The 2%/2 mm γ passing rates were 98.05%, 97.92%, and 98.31% for the cycleGAN, CUT, and denseCUT, respectively.Conclusions:DenseCUT can generate more accurate pseudo-CT images and the pseudo-CT can meet the demand for the dose calculation of IMRT plan.

Observation on iodine metabolism in milk of lactating rats with different iodine nutritional levels / 中华地方病学杂志

Objective:To observe the urinary iodine content (UIC), breast milk iodine content (BMIC) and milk iodine excretion of lactating rats under different iodine nutrition levels, and to explore the iodine metabolism of the lactating rats under different iodine nutrition levels.Methods:Forty female Wistar rats with body weight ranging from 70 to 120 g were divided into low iodine (LI) group, normal iodine (NI) group, hight iodineⅠ (HIⅠ) group and hight iodine Ⅱ (HIⅡ) group according to body weight by random number table method, with 10 rats in each group. The rats were fed low-iodine diet, and the iodine ion concentration of drinking water in each group was 0, 325, 18 700 and 37 450 μg/L. Twenty male rats were fed according to the feed method of NI group. After 8 weeks of intervention, the male and female rats were caged and mated in a ratio of 1 ∶ 2. Milk and 24 h urine were collected on the 7th, 14th and 21st days of lactation (L7, L14 and L21), and the amount of food and drinking water consumed were recorded. The 24 h milk excretion was calculated by acute lactation test. UIC and BMIC were determined by inductively coupled plasma mass spectrometry (ICP-MS).Results:The 24 h total iodine intake of lactating rats in LI, NI, HIⅠ and HIⅡ groups were (1.84 ± 0.51), (30.51 ± 6.79), (765.95 ± 317.41) and (1 654.26 ± 560.55) μg/d, respectively. The difference between groups was statistically significant ( P < 0.001). At L7, L14 and L21, there were statistically significant differences in UIC, BMIC and milk iodine excretion at the same lactation stages among different groups ( P < 0.001). In HIⅡ group, the difference of BMIC and milk iodine excretion at different lactation stages (L7, L14, and L21) were significantly signrficant ( P < 0.05). The 24 h milk iodine excretion of LI, NI, HIⅠ and HIⅡ groups was (1.23 ± 0.85), (11.88 ± 5.23), (207.09 ± 114.51), (493.67 ± 242.47) μg, respectively. The proportion of 24 h milk iodine excretion to 24 h total iodine intake was 66.85%, 38.94%, 27.04% and 29.84%, respectively. Conclusions:About 39% of dietary iodine is supplied to offspring through milk when iodine nutrition is normal. The iodine excretion ratio of milk is increased or decreased with low and high iodine levels. These results indicate that lactating rats with different iodine nutrition levels can regulate the ratio of iodine excretion in milk through their own compensatory effect to reduce the influence of iodine deficiency and iodine excess on their offspring.

Ultrasmall nanoprobe in MR/CT bimodal imaging for tumor angiogenesis / 中华核医学与分子影像杂志

Objective:To fabricate tAu@glutathione(GSH)@Gd nanoprobe for tumor angiogenesis bimodal (MR/CT) imaging, and evaluate its characteristics and potential for MR/CT imaging in vivo. Methods:The tAu@GSH@Gd nanoprobes were constructed by encapsulating Au and Gd atoms into the GSH shell with cyclic asparagine-glycine-arginine (cNGR) peptide conjugation. EMT-6 BALB/c mice subcutaneous transplantation tumor models were established ( n=30) and divided into blank control group (saline), control group (Au@GSH@Gd nanoparticles) and experimental group (tAu@GSH@Gd nanoprobes) ( n=10 in each group). In vivo MR/CT imaging and distribution study were performed at different time points after tail intravenously injection. Relative MR signal value and relative CT value of tumor site and main organs in mice were used to evaluate MR/CT imaging property and biological distribution. After that, tumor tissues were collected for silver staining to study the accumulation of Au@GSH@Gd nanoparticles and tAu@GSH@Gd nanoprobes. Independent-sample t test was used for data analysis. Results:The tAu@GSH@Gd nanoprobes were (6.40±0.22) nm with high T 1 relaxation efficiency ((36.91±0.07) mmol·L -1·s -1). MR/CT imaging of tAu@GSH@Gd nanoprobes showed good performance in vitro. In vivo MR/CT imaging demonstrated MR/CT imaging of tumor was significantly enhanced by tAu@GSH@Gd nanoprobes after 2 h post injection. The strongest enhancement was observed at 24 h, with an increased relative MR signal value from 1.04±0.12 (before injection) to 1.84±0.26 ( t=12.61, P=0.006), and increased relative CT value from 1.01±0.04 (before injection) to 1.95±0.05 ( t=15.34, P=0.004). The highest MR/CT effect in control group appeared at 16 h, with the relative MR signal value of 1.50±0.06 and the relative CT value of 1.53±0.10, which were significantly lower than those in experimental group (1.84±0.26 and 1.95±0.05; t values: 5.35 and 16.46, both P<0.05). Distribution in normal tissues showed that most of tAu@GSH@Gd nanoprobes were metabolized through the kidneys. Tissue silver staining experiment verified the tumor angiogenesis targeting effect. Conclusion:The tAu@GSH@Gd nanoprobes exhibit favorable tumor angiogenesis target MR/CT imaging ability, providing a new design concept and basis for assessing tumor angiogenesis.

Incidence and Mortality of Male Breast Cancer in Hubei Province from 2012 to 2015 / 肿瘤防治研究

Objective To analyze the incidence and mortality of male breast cancer in Hubei Province from 2012 to 2015. Methods The data reported by the Hubei Provincial Cancer Registry from 2012 to 2015 were collected for analyzing the incidence and mortality trends of male breast cancer according to year, urban and rural areas and age. We also compared the difference of incidence and mortality between male and female breast cancer. Results A total of 106 new cases of male breast cancer were reported in Hubei Cancer Registry from 2012 to 2015 with an incidence rate of 0.43/105, and 10052 new cases of female breast cancer with an incidence rate of 42.76/105; the male-to-female incidence ratio was 1:99. Male breast cancer death cases was 37 with the death rate of 0.15/105, and female breast cancer death cases was 2201 with the death rate of 9.36/105; the male-to-female mortality ratio was 1:62. The incidence and mortality of breast cancer between male and female varied by year, urban and rural areas. Male breast cancer was less common in young men (< 35 years old), and the incidence increased with age after 35 years old; male breast cancer deaths were rare in men under 45 years old, and the mortality rate increased with age. The incidence and mortality of male breast cancer patients over 85 years old reached the peak. Conclusion Male breast cancer is rare in clinical practice, and the incidence rate is much lower than that of female breast cancer. Even so, it is necessary to study the epidemiological law of male breast cancers' incidence and mortality, which can be used for prevention and treatment of male breast cancer.

The effect of calcium acetate in treatment of elderly patients with CAPD in peritoneal dialysis patients with hyperphosphatemia and efficacy / 中国生化药物杂志

Objective To investigate the effect of calcium acetate in treatment of elderly patients with CAPD in peritoneal dialysis patients with hyperphosphatemia and efficacy.MethodsFrom March 2013 to January 2016,46 elderly patients with CAPD were randomly divided into experimental group and control group.The control group were used calcium 1.5mmol/L Liquor Dialysisintraperitoneus CAPD treatment,and control diet.Besides these treatments,the experimental group were given calcium acetate tablets 668mg/3 times every day after a meal, 2 tablets each time.All patients were detected before treatment and 4,6 and 10 weeks after the serum calcium, phosphorus and calcium and phosphorus in blood iPTH index, calculate the product of calcium and phosphorus,record and statistical analysis.ResultsTwo groups after 4 week of treatment, all outcome measures were decreased;the experimental group blood phosphorus decreased significantly after 6 weeks treatment;it after 10 weeks of treatment, serum calcium(t=5.202),phosphorus(t=7.767),blood iPTH(t=-10.324) and the calcium phosphorus product (t=-4.106) compared with that before treatment,there were statistically significant differences(P<0.01);the control group after 10 weeks of treatment, with all outcome measures there were no significant differences.The experimental group after 10 weeks of treatment,serum calcium(t=-4.055),phosphorus (t=-9.037),blood iPTH(t=9.940) and the calcium phosphorus product(t=-4.211)compared with the control group,the differences were statistically significant(P<0.01).ConclusionCalcium acetate treatment can significantly reduce the blood serum of aged CAPD in peritoneal dialysis patients with high phosphorus,effectively prolong the survival time and improve the quality of life during treatment.

Effects of prednisone on renal FAK and Pyk2 expressions in rats with adriamycin- induced nephritis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of prednisone on the expressions of FAK and Pyk2 in the kidneys of rats with adriamycin-induced nephritis.</p><p><b>METHODS</b>Thirty SD rats were randomized into normal control group, adriamycin-induced nephritic model group, and prednisone treatment group (n=10). Prednisone was administered at 10 mg/kg once daily in nephritic rats starting since the 7th day after adriamycin injection. Twenty-four-hour proteinuria was measured in the rats at different time points, and renal tissue histology was examined using transmission electron microscope. The expression levels of Pyk2, FAK and nephrin mRNA in the renal tissue were detected tested by RT-PCR, and the protein expressions of FAK, Pyk2, phosphorylated Pyk2 and phosphorylated FAK-Tyr397 were detected by Western blotting; immunohistochemistry was used for detecting nephrin protein expression in the kidney.</p><p><b>RESULTS</b>Compared with the normal control group, the rats with adriamycin-induced nephritis showed significantly increased proteinuria (P<0.01), which was obviously lowered by prednisone treatment (P<0.01). Transmission electron microscopy revealed extensive fusion of the foot processes of the podocytes in the model group. Prednisone treatment promoted nephrin expression in the kidney (P<0.05). Compared with the control group, the model and prednisone treated groups showed significantly lowered nephrin mRNA expression (P<0.01) but increased FAK mRNA expression (P<0.01), but prednisone-treated group had a higher nephrin mRNA expression than the model group (P<0.05). The model group exhibited significantly increased expressions of FAK total and phosphorylated proteins, P-FAK/FAK, and P-Pyk2/Pyk2 (P<0.01), which were all lowered in the treatment group (P<0.01). Correlation analysis suggested that the expressions of FAK mRNA, FAK, pFAK, Pyk2 mRNA and pPyk2/Pyk2 were positively correlated with proteinuria (r=0.819, 0.750, 0.838, 0.762, 0.934, respectively, P<0.01).</p><p><b>CONCLUSIONS</b>Adriamycin increases phosphorylated FAK and Pyk2 expressions to mediate kidney injury in rats. Prednisone inhibits Pyk2 and FAK activation, decreases proteinuria, and alleviates podocyte lesions to protect the glomerular filtration barrier.</p>

Isolation and in vitro propagation of aldehyde dehydrogenases positive breast cancer stem cells and investigation on biological property of these cells / 肿瘤研究与临床

Objective To identify a aldehyde dehydrogenases positive (ALDH+) cancer stem cell subpopulation in MCF-7 cells and to investigate the proliferation and differentiation characteristics of these cells in vitro.Methods ALDH+ breast cancer stem cells were isolated from MCF-7 cells by flow cytometry and the biological property of ALDH+ breast cancer stem cells were examined by scarification test,MTT,growth curvature and Transwell migration assay.Results The ratio of CD-/low24 CD+44 cells was about 1.4 ％ in MCF-7 cells.The ratio of ALDH+ CD-/low24CD+44 cells was about 1.2 ％.The growth curvature of ALDH+ breast cancer stem cells was almost the same with that of CD-/low24 CD+44 cells.The distance between cells was obviously shorter in both CD-/low24 CD+44 cells scarification zone and ALDH+ CD-/low24 CD+44 cells scarification zone.The migration ability of CD-/low24CD+44 cells and ALDH+ CD-/low24CD+44 cells was stronger than control group cells.There were migration ability differences between CD-/low24CD+44 cells and ALDH+ CD-/low24CD+44 cells.The results of Transwell experiments were in coincidence with above results.Lots of CD-/low24CD+44 cells and ALDH+ CD-/low24CD+44 cells were through the membrane.In MTT assay,absorbance values were 1.05±0.098,1.56±0.075 and 1.67±0.032.Conclusion CD--/low24CD+44 and ALDH+ CD-/low24CD+44 breast cancer stem cell subpopulation exist in MCF-7 cells.ALDH could potentially be used as a molecular marker to identify breast cancer stem cell subpopulation.

Strategy of breast reconstruction for patients with caesarotomy scar using pedicled TRAM flap / 中华医学美学美容杂志

Objective To investigate the availability and strategy of breast reconstruction for patients with caesarotomy scar using pedicled TRAM flap.Methods From January 2007 to May 2011,12 cases of breast reconstruction with caesarotomy scar were carried out with pedicled TRAM flaps.All the patients that were classified as the class Ⅱ that was 0.5 or less by score were operated on by using the inverted trapezoid incision,of which the upper edge was 2 or 3 cm down to the umbilicus.Double pedicles were adopted for the patient with the longest vertical scar; single pedicle of the breast contralateral side and the muscle sheath of the breast ipsilateral side were harvested for the rest of the patients.A synthetic mesh was used for the enforcement of the muscle and sheath defect.Results No flap necrosis or abdominal complications were observed.With the follow-up from 3 months to 4 years and 4 months,the overall satisfactory rate was 100 ％.Conclusions The strict patient selection and the operating strategy are the keys to the successful breast reconstruction for patients with caesarotomy scar using pedicled TRAM flap.

Clinical study of the axillary conservative surgery by sentinel lymph node biopsy using preoperative lymphoscintigraph technique with 99mTc-SC and methylene blue in breast cancer surgical therapy / 中国医师进修杂志

Objective To evaluate the clinical significance of the axillary conservative surgery by sentinel lymph node biopsy (SLNB) using preoperative lymphoscintigraph technique with 99mTc-SC and methylene blue in early-stage breast cancer patients. Methods The sentinel lymph node (SLN) of 187 patients were located with preoperative lymphoscintigraph technique with 99mTc-SC and labeled with methylene blue during the operations. The metastasis of SLN was detected using frozen section technique. There were 51 patients whose SLN were positive having been carried with modified radical mastectomy of breast cancer and axillary lymph node dissection (ALND), 136 patients' SLN were negative,58 patients of those were carried with mammectomy or partial mastcctomy and ALND (group A),while 78 patients were carried out with mammectomy or partial mastectomy only (group B). The sentinel lymph nodes were detected with HE stain after surgery. All the patients were treated with chemotherapy,and the patients with partial mastcctomy must be treated with radiotherapy. There were 2 patients with micrometastasis in group B being treated with mammectomy or partial mastcctomy only,and carried out with ALND again. Results The number of cases with upper limb numbness, edema, dysfunction in group A were 36,8 and 45 cases, in group B were 2,0,0 case respectively. Group A compared with group B was increased significantly (P 0.05). Conclusion It is simple and accurate to carry out SLNB using preoperative lymphoscintigraph technique with 99mTc-SC combined with methylene blue,and the effect is reliable.

The clinical observation of treating leukopenia which is caused by antivirus medicines by diyushengbai tablet / 中国基层医药

Objective To observe the curative effect of treating leukocyte decreasing of parts of chronical hepatitis B or hepatitis C caused by interferon by diyushengbai tablet.Methods 57 subjects of patients were divided into two groups randomly,the research group:30 subjects were cured by diyushengbai tablet,and the control group:27 subjects were cured by vitami B_4.Both of their course of treatment were two weeks.Then total effective rates of leukocyte count in peripheral blood were compared before treatment and after treatment.Results The leukocyte in research group raised much more obviously than the control group,and the total effective rates separately were 83.33%(25/30) and 70.37%%(19/27),there was notable diversity(P

Oophorectomy combined with exemestane treating advanced refractory breast cancer / 中国癌症杂志

Background and purpose:Tamoxifen is the main endocrine therapy of premenopausal breast cancer with positive hormone receptors but numerous patients have developed advanced refractory breast cancer due to drug resistance.Our study investigated the role of combining oophorectomy and exemestane in the treatment of advanced refractory breast cancer.Methods:Oophorectomy was carried out in all patients.Exemestane was administered orally (25 mg/d) one week after the operation.The median time of progression (TTP),the median survival time as well as the survival rate were calculated using the Kaplan-Meier methods.Results:Seventeen patients ranging between the ages of 26 and 44 years (median:36 years) were treated resulting in an overall response rate of 64.70%,TTP was 8 months and the median survival time was 31 months.The survival rates for 1 year,3 years and 5 years were 88.24%,64.71%,29.41%,respectively.No grade Ⅲ and Ⅳ side effects appeared.Conclusion:Oophorectomy when combined with exemestane showed antitumor activity for advanced refractory premenopausal breast cancer through positive hormone receptor and it is also well-tolerated.

Morphologic Relationship between the Pontine Micturition Center and the Sympathetic Center in the Spinal Cord of the Rat / 华中科技大学学报（医学）（英德文版）

Summary: To study whether the sympathetic nerves coordinate with the parasympathetic nerves during micturition in the rat. We used antegrade neural tracing with biotinylated dextran amine (BDA) injected into the pontine micturition center (PMC) to label the terminals in the L6-S1 cord. Preganglionic parasympathetic neurons (PPNs) in the L6-S1 segment were labelled by retrograde transport of Fluorogold (FG) from the major pelvic ganglion (MPG).We detected retrograde neurons in L6-S1 using retrograde transport of horseradish peroxidase (HRP) from the intermediolateral cell column (IML) of the L1-L2 segment where sympathetic preganglionic neurons (SPNs) are located. Immunohistochemical methods showed that PPNs were identified to be choline acetyltransferase-immunoreactive (ChAT-IR). HRP-labelled neurons were not ChAT-IR and located dorsal to PPNs. BDA-labelled terminals were located mainly in the bilateral IML of L6-S1, some of which had synaptic contact with the HRP-labelled neurons. In addition, there were some wheat germ agglutinin-horseradish peroxidase (WGA-HRP) labelled terminals in the ipsilateral IML of the L1-L2 segment after WGA-HRP was microinjected into SPN. We conclude that PMC may control the preganglionic neurons of sympathetic nerves through the interneurons located dorsal to PPNs.