OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

Objective To investigate how tumor-associated macrophages(TAMs)in cervical cancer cells respond to AMPK through phenotypic transformation.Methods RT-qPCR and Western blot were used to detect AMPK expression in cervical cancer tissues and HeLa,SiHa and Caski cell lines.The AMPK knockout cell line of HeLa cells was generated using the siRNA technique.The malignant biological behavior of cancer cells mediated by the AMPK/CCL18 axis was investigated using CCK-8,scratch assay and Transwell assay.Cell conditioned medium from each group was collected,and cervical cancer cell conditioned medium was co-cultured with human mononuclear cells(THP-1)to assess THP-1 recruitment and the expression of macrophage typing related markers.The impact of AMPK on tumor proliferation was also evaluated in nude mice.Results QRT-PCR and Western blot analysis showed that the mRNA(1.78±0.30)and protein(1.71±0.33)expression levels of AMPK in cancer tissues were significantly higher than those in adjacent tissues(1.00±0.10,1.00±0.11),and the differences were statistically significant(t=5.966,4.990,all P<0.01).Compared with normal cervical epithelial cells(HUCEC),the mRNA and protein expression of AMPK were significantly increased in three cell lines(HeLa,SiHa,Caski),and the differences were statistically significant(F=5.958,3.457,all P<0.01).Compared with the NC group,knocking down AMPK inhibited the proliferation of cervical cancer cells(1.33±0.18 vs 0.82±0.25),migration(180.07±7.64 vs 126.98±29.00),and invasion(115.90±13.19 vs 68.61±12.87)in cervical cancer cells,with statistical significance(t=4.015,4.337,6.285,all P<0.01).The study found that THP-1 cells exhibited significant reductions in migration(49.34±3.91 vs 33.96±10.94),invasion(28.54±3.06 vs 19.54±6.16)and M2-type polarization(1.01±0.13 vs 0.55±0.11)when AMPK reduction was induced,and these differences were statistically significant(t=3.242,3.207,6.510,all P<0.01).In vivo experiments further supported these findings,showing that AMPK reduction led to significant decreases in tumor volume(721.56±93.70mm3 vs 520.02±47.54mm3)and weight(1.19±0.06g vs 0.86±0.20g),with statistically significant differences(t=4.289,3.582,P<0.01).Conclusion Through modulating M2 polarization in TAMs,the AMPK/CCL18 axis increases cervical cancer cells'proliferation,migration and invasion.AMPK/CCL18 inhibition could provide novel therapeutic targets and approaches for cervical cancer treatment.

Objective To investigate how tumor-associated macrophages(TAMs)in cervical cancer cells respond to AMPK through phenotypic transformation.Methods RT-qPCR and Western blot were used to detect AMPK expression in cervical cancer tissues and HeLa,SiHa and Caski cell lines.The AMPK knockout cell line of HeLa cells was generated using the siRNA technique.The malignant biological behavior of cancer cells mediated by the AMPK/CCL18 axis was investigated using CCK-8,scratch assay and Transwell assay.Cell conditioned medium from each group was collected,and cervical cancer cell conditioned medium was co-cultured with human mononuclear cells(THP-1)to assess THP-1 recruitment and the expression of macrophage typing related markers.The impact of AMPK on tumor proliferation was also evaluated in nude mice.Results QRT-PCR and Western blot analysis showed that the mRNA(1.78±0.30)and protein(1.71±0.33)expression levels of AMPK in cancer tissues were significantly higher than those in adjacent tissues(1.00±0.10,1.00±0.11),and the differences were statistically significant(t=5.966,4.990,all P<0.01).Compared with normal cervical epithelial cells(HUCEC),the mRNA and protein expression of AMPK were significantly increased in three cell lines(HeLa,SiHa,Caski),and the differences were statistically significant(F=5.958,3.457,all P<0.01).Compared with the NC group,knocking down AMPK inhibited the proliferation of cervical cancer cells(1.33±0.18 vs 0.82±0.25),migration(180.07±7.64 vs 126.98±29.00),and invasion(115.90±13.19 vs 68.61±12.87)in cervical cancer cells,with statistical significance(t=4.015,4.337,6.285,all P<0.01).The study found that THP-1 cells exhibited significant reductions in migration(49.34±3.91 vs 33.96±10.94),invasion(28.54±3.06 vs 19.54±6.16)and M2-type polarization(1.01±0.13 vs 0.55±0.11)when AMPK reduction was induced,and these differences were statistically significant(t=3.242,3.207,6.510,all P<0.01).In vivo experiments further supported these findings,showing that AMPK reduction led to significant decreases in tumor volume(721.56±93.70mm3 vs 520.02±47.54mm3)and weight(1.19±0.06g vs 0.86±0.20g),with statistically significant differences(t=4.289,3.582,P<0.01).Conclusion Through modulating M2 polarization in TAMs,the AMPK/CCL18 axis increases cervical cancer cells'proliferation,migration and invasion.AMPK/CCL18 inhibition could provide novel therapeutic targets and approaches for cervical cancer treatment.

Objective To investigate the prevalence of thyroid nodules and thyroid dysfunction in southern mountainouss areas of Ningxia.Methods A cross-sectional study was conducted among a representative sample of 10 639 adults in Jingyuan county with a population proportionate sampling method.High-resolution ultrasound was used to examine the thyroid and fasting blood specimens were collected in the morning for measurement of TSH,FT4,FT3.Chi-square test and spearman rank correlation analysis were used for statistical analysis.Results The prevalence of thyroid nodules was 29.08％,the sex-and age-adjusted rate was 27.17％.The prevalence of thyroid nodules was higher in women than in men (32.68％ vs.24.88％,x2=76.029 2,P＜0.001) and age was positively associated with thyroid nodules (r=0.272,P＜0.001).The rate of thyroid dysfunetion,subclinical hypothyroidism,subclinical hyperthyroidism,hypothyroidism,hyperthyroidism were 17.39％,13.00％,0.42％,0.96％,3.01％,respectively.The prevalence of thyroid nodules was higher in abnormal TSH group than in normal TSH group (39.44％ vs.27.24％,x2=95.624 0,P＜0.001).The level of THS,FT3,FT4 in thyroid nodules group differed fromn control group (Z=-9.144,P＜0.001;Z=-6.140,P＜0.001;Z=-1.997,P=0.046).Conclusion The prevalence of thyroid nodules and thyroid dysfunction were higher in southern mountainous areas of Ningxia.The relationship between thyroid nodules and thyroid function needs further research.We should pay attention to the early screening and diagnosis of thyroid nodules in mountainous areas.

Objective To investigate the predictive value of metabolic tumor volume (MTV) in angiogenesis and hematoge‐nous metastasis of patients with colorectal cancer .Methods Totally 108 patients with colorectal cancer from January 2011 to De‐cember 2015 were enrolled into the study and divided into metastasis group (n=42) and non‐metastasis group (n=66) according to whether combining with hematogenous metastasis .All patients received 18 F‐2‐fluoro‐D‐glucose positron emission tomography/com‐puted tomography (18F‐FDG PET/CT) before operation ,then used the PET VERA software to automatically calculate MTV ac‐cording to the 40% of standard uptake value max(SUVmax ) as the threshold .The blood vessels were identified with CD34+ immu‐nohistochemical staining ,then measured the microvessel density (MVD) .The clinical pathologic data ,SUVmax ,MTV and MVD were compared between metastasis group and non‐metastasis group .The area under the receiver‐operating characteristic curve (AUC) was performed to evaluate the predictive value of MTV on hematogenous metastasis .Results SUVmax ,MTV and MVD in metastasis group were significantly higher than that in non‐metastasis group (P<0 .05) .There were significant differences in MTV and MVD among patients with different T stage (P<0 .05) .Pearson correlation analysis results showed that MTV was positively correlated with MVD (r=0 .636 ,P<0 .001) ,and there was no significant relationship between MTV and SUVmax (r= 0 .161 ,P=0 .096>0 .05) ,MVD and SUVmax (r=0 .179 ,P=0 .064>0 .05) .AUC of MTV was 0 .736 ,and the best threshold value was 15 .016 cm3 ,whose sensitivity ,specificity ,positive predictive value ,negative predictive value and Youden index were 83 .3% ,63 .6% , 59 .3% ,85 .7% and 47 .0% respectively .Conclusion Compared with SUVmax ,MTV of colorectal cancer is associated with angio‐genesis and hematogenous metastasis ,so as to predict the prognosis of colorectal cancer ,which is worthy of clinical application .

BACKGROUND: Magnesium alloy studies in orthopedic field have been carried out,and good biocompatibility has been reported.However magnesium alloys have not yet been researched in the intestine.OBJECTIVE: The biodegradable magnesium-zinc alloy samples are implanted around the rat cecum to investigate the biocompatibility in rat.METHODS: Sprague Dawley rats were randomly divided into magnesium alloy group,medical titanium group and the sham-operated group.Then magnesium-zinc alloy samples with the dimension of 5 mm × 1 mm× 1 mm were embedded in the cecum incision in the magnesium alloy group.The medical titanium was embedded in the medical titanium group,and just suture in the sham-operated group.Prior to surgery and at 7,14,21 and 28 days after operation,the serum glutamic-oxaloacetic transaminase,creatinine and magnesium ion concentration were examined in each group.X-ray film on implanted region.The pathological changes in liver,kidney and cecum were examined.RESULTS AND CONCLUSION: There were no significant differences in serum glutamic-oxaloacetic transaminase,creatinine and magnesium ion concentrations among each group(P > 0.05).Magnesium-zinc alloy degraded gradually during 28 days.The pathology of liver,kidney and cecum was normal.Results suggested that magnesium-zinc alloy had no obvious effect on the cecum.The degradation time to play a fixed function of time was longer than the intestinal healing time,with good biocompatibility.Magnesium-zinc alloy can be used as anastomotic nail for stomach intestine anastomat.

Objective To investigate the effects of caveolin-1 overexpressing on the growth of cervical squamous cell cancer Hela cell line. Methods Eukaryotic expression vector of human caveolin-1 gene was introduced into Hela cells by Lipofectamine. The clones stably overexpressed caveolin-1 were identiffed by RT-PCR, immunofluorescence cell staining techniques and Westernblotting. Cells proliferation viabihty was tested by MTT assay, and flow cytometry was used to assay the cell cycle and apoptosis, and the relative phosphorylation level of extracellular regulated protein kinases (Erk1/2) were detected by Westernblotting. Results The clones stably overexpressed caveolin-1 were obtained. Compared with the parental Hela cells, the tranfected cells exhibited a slower rate of growth. FAGS analysis results revealed that overexpression of caveolin-1 resulted in the cell cycle arrest in the G0/G1 [ ( 68. 04 ± 2. 57 ) % vs ( 53.41 ±1.01)%] phase and increased the apoptotic cell fraction[ (19. 18 ±2.20)% vs (5.63 ±0.55)%, P <0. 05 ]. Western blotting results showed that overexpression of caveolin-1 reduced the phosphorylation of Erk1/2(0.28 ±0.05 vs 0.81 ±0.07, P <0.05). Conclusions Overexpression of caveolin-1 suppressed the growth of Hela cells and induced apoptosis, down-regulation of Erk1/2 phosphorylation might be involved in its mechanism.

Apoptosis is a spontaneous process of cell-suicide process triggered in response to physiological and pathological stress stimul, which is to regulate the developmental of body, control cell senescence, maintain a stable internal enviroment in multicellular organisms. The initial and progress of apoptosis is precisely controlled, which is a unique and complex signal system. In this review, it introduced the relationship between apoptosis and bcl-2 gene family, C-myc, tumor suppressor gene p53, Caspase protease family and Fas, and Summaries the detection methods.