Nanomedicine-based multimodal therapies: Recent progress and perspectives in colon cancer.

Colon cancer has attracted much attention due to its annually increasing incidence. Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic side effects. In the past decade, nanomedicines with multimodal therapeutic strategies have shown potential for colon cancer because of their enhanced permeability and retention, high accumulation at tumor sites, co-loading with different drugs, and comb-ination of various therapies. This review summarizes the advances in research on various nanomedicine-based therapeutic strategies including chemotherapy, radiotherapy, phototherapy (photothermal therapy and photodynamic therapy), chemodynamic therapy, gas therapy, and immunotherapy. Additionally, the therapeutic mechanisms, limitations, improvements, and future of the above therapies are discussed.

[Small splint external fixation combined with 3D printing brace for the treatment of Colles fractures].

OBJECTIVE: To explore the short-term clinical efficacy of manipulation reduction-combined with small splint and 3D printing wrist brace external fixation of wrist brace for Colles fracture and the advantages of using the brace. METHODS: A total of 60 patients with Colles fractures who were treated in Zhongshan Hospital of Traditional Chinese Medicine from February to December 2017 were selected. Patients were randomly divided into 2 groups according to the order of treatment, with 30 patients in the control group, including 13 males and 17 females, aged from 16 to 66 years, with a mean of (49.46±12.63) years; the time from injury to consultation ranged from 3 to 18 h, averaged (6.86±3.15) h. In the experimental group, there were 30 cases, 12 males and 18 females, ranging in age from 14 to 68 years old, with a mean of (46.73±14.40) years old; the time from injury to consultation ranged from 3 to 19 h, averaged(7.06±3.45)h. All the patients in the experimental group and the control group were treated with the same doctor's manipulation to reduce the fracture. The small splints were applied for external fixation after the satisfactory reduction shown in the X-ray. After 1 week of fracture treatment, the small splints were removed from the patients in the experimental group and the 3D printing braces were replaced to maintain fixation until the fracture healed. In the control group, small splints were maintained until the fracture healed. Wrist joint X-ray films were taken before and after reduction and 4 weeks after reduction to observe the palmar inclination angle, ulnar deviation angle, radius height and compare; VAS score and swelling degree score were recorded before and after reduction for 1 and 2 weeks; Cooney and PRWE score of wrist joint were compared after 6 to 8 weeks of reduction. RESULTS: The VAS score of 2 weeks after reduction was 2.40±0.49 in the experimental group and 2.43±0.50 in the control group. There was no statistical difference in the VAS score between the two groups before and after reduction(P=0.364). The swelling degree of 2 weeks after reduction was 0.50±0.50 in the experimental group and 0.53±0.50 in the control group. There was no statistical difference in the swelling degree between the two groups before and after reduction(P=0.746). The Cooney and PRWE scores of the experimental group were better than those of the control group 6 to 8 weeks after reduction (P<0.05), and the anatomical characteristics of palmar inclination, ulnar deviation and radial shortening of the experimental group were better than those of the control group(P<0.05). CONCLUSIONS: 3D printing braces are light and breathable, comfortable and beautiful, and convenient for dressing. The combination of small splint sequentially applied to Colles fracture has a definite clinical effect, which enriches the means of external fixation treatment. It is believed that with the deepening of clinical research, the design and materials of 3D printing braces as well as their application in future medical treatment will be further developed.

Prognostic analysis of different morphology of the necrotic-viable interface in osteonecrosis of the femoral head.

PURPOSE: The purpose of this study was to investigate the collapse progression in different morphologies of the necrotic-viable interface in osteonecrosis of the femoral head (ONFH). METHODS: A total of 168 patients (202 hips) with Association Research Circulation Osseous (ARCO) stage II ONFH were included. Ending with the collapse of the femoral head, all patients received conservative treatment but without surgical intervention and were followed for three to 91 months. Bilateral hip-joint radiographs and magnetic resonance imaging (MRI) were examined, and the largest layer of necrosis within the coronal section of MRI images was selected together with its anteroposterior radiograph to observe the morphology of the necrotic-viable interface. The morphology was divided into four types: I, type transverse; II, type "V"; III, type zigzag; IV, type closed. The collapse rate and the time to collapse in different morphologies were assessed. RESULTS: A total of 120 hips collapsed in two years or less, 61 were type-I, 51 were type-II, and 8 were type-III. Non-collapse occurred in all 17 hips with type-IV ONFH during long-term follow-up. In 202 hips with ARCO stage-II ONFH, the collapse rate in type-I ONFH was significantly higher than that of type-II and type-III ONFH (P < 0.01 for both). The time to collapse was markedly shortened. CONCLUSIONS: The risk of ONFH-induced collapse is influenced by the morphology of the necrotic-viable interface. Effective mechanical support for preventing the collapse of the femoral head is necessary when the morphology of the necrotic-viable interface is type transverse.

Detecting dopaminergic neuronal degeneration using diffusion tensor imaging in a rotenone-induced rat model of Parkinson's disease: fractional anisotropy and mean diffusivity values.

Dopamine content in the basal ganglia is strongly associated with the degree of dopaminergic neuron loss in the substantia nigra pars compacta. Symptoms of Parkinson's disease might not arise until more than 50% of the substantia nigra pars compacta is lost and the dopamine content in the basal ganglia is reduced by more than 80%. Greater diagnostic sensitivity and specificity would allow earlier detection of Parkinson's disease. Diffusion tensor imaging is a recently developed magnetic resonance imaging technique that measures mean diffusivity and fractional anisotropy, and responds to changes in brain microstructure. When the microscopic barrier (including cell membranes, microtubules and other structures that interfere with the free diffusion of water) is destroyed and extracellular fluid volume accumulates, the mean diffusivity value increases; when the integrity of the microstructure (such as myelin) is destroyed, fractional anisotropy value decreases. However, there is no consensus as to whether these changes can reflect the early pathological alterations in Parkinson's disease. Here, we established a rat model of Parkinson's disease by injecting rotenone (or sunflower oil in controls) into the right substantia nigra. Diffusion tensor imaging results revealed that in the stages of disease, at 1, 2, 4, and 6 weeks after rotenone injection, fractional anisotropy value decreased, but mean diffusivity values increased in the right substantia nigra in the experimental group. Fractional anisotropy values were lower at 4 weeks than at 6 weeks in the right substantia nigra of rats from the experimental group. Mean diffusivity values were markedly greater at 1 week than at 6 weeks in the right corpus striatum of rats from the experimental group. These findings suggest that mean diffusivity and fractional anisotropy values in the brain of rat models of Parkinson's disease 4 weeks after model establishment can reflect early degeneration of dopaminergic neurons. The change in fractional anisotropy values after destruction of myelin integrity is likely to be of greater early diagnostic significance than the change in mean diffusivity values.

[Exposure Level of Population and Economy in Zhejiang Province Considering the Background of PM2.5 in East China].

Using the satellite-derived Fine Particulate Matter (PM2.5) data of global high-precision products during 1998-2012, detailed characteristics of PM2.5 distribution over East China and its change are given, and the PM2.5 exposure levels for population and economy in Zhejiang is further analyzed in this context. The results show that the overall variability of the regional average value of PM2.5 concentration exhibits an increasing trend followed by a decrease during 1998-2012, which is consistent in both the East China and Zhejiang provinces; the turning point occurs around 2007-2009. In the initial years (1998-2000), annual average PM2.5 concentrations are below 50 µg·m-3 in the southern part of East China and eastern part of Shandong, while it is 50-75 µg·m-3 in other areas. During this period, 51.8% of the area in East China and 21.1% of the area in Zhejiang have PM2.5 concentrations larger than 35 µg·m-3 (Air quality standard value in China). The rising trend in PM2.5 concentration is extremely obvious in 1998-2009; the mean linear trend over East China is 2.58 µg·(m3·a)-1, while it is 1.43 µg·(m3·a)-1 over Zhejiang province. PM2.5 concentration reaches its maximum during 2007-2009. The area where PM2.5 concentration is larger than 35 µg·m-3 reaches 82.1% in East China and 65.9% in Zhejiang province. After that, the PM2.5 concentration begins to decrease in each region, and the average change trend in East China and Zhejiang are -1.75 µg·(m3·a)-1 and -1.58 µg·(m3·a)-1, respectively. The regional area in which PM2.5concentrations aregreater than 35 µg·m-3 displays a slight decline during 2010-2012, which suggests that the energy conservation and emission reduction plan proposed by the Chinese government and associated measures may play a vital role in improving air quality of East China. In 2010, the proportion of the population and GDP for which the PM2.5 exposure level exceeded 35 µg·m-3 were 74.0% and 70.8%, respectively, of which 38.1% of the population lives in an environment where annual average PM2.5 concentrations are more than 50 µg·m-3. In addition, 38.9% of the GDP is produced in an environment with annual average PM2.5 concentrations more than 50 µg·m-3.

Protective effects of two Lactobacillus plantarum strains in hyperlipidemic mice.

AIM: To investigate the effects of Lactobacillus plantarum (L. plantarum) CAI6 and L. plantarum SC4 on hyperlipidemic mice. METHODS: Male Kunming mice were fed a high-cholesterol diet for 28 d to construct hyperlipidemic models. Hyperlipidemic mice and normal mice were assigned to 3 groups which were separately treated with L. plantarum CAI6, L. plantarum SC4, and physiological saline through oral gavage for 28 d. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured by commercially available enzyme kits. FACS Calibur flow cytometry was used to examine hepatic and renal nuclear factor-erythroid 2-related factor 2 (Nrf2) expression. The morphology of livers was checked by hematoxylin and eosin staining and optical microscope observation. RESULTS: Compared with normal mice, hyperlipidemic mice possessed significantly higher TC (3.50 ± 0.43 vs 2.89 ± 0.36, P < 0.01), TG (1.76 ± 0.07 vs 1.10 ± 0.16, P < 0.01), and LDL-C (1.72 ± 0.20 vs 0.82 ± 0.10, P< 0.01) levels, resulting in an increase of atherogenic index (AI) (2.34 ± 1.60 vs 0.93 ± 0.55, P < 0.05) and LDL-C/HDL-C ratio (1.43 ± 0.12 vs 0.51 ± 0.16, P < 0.05). After treatment with L. plantarum CAI6/L. plantarum SC4, TG (1.43 ± 0.27/1.54 ± 0.10 vs 1.76 ± 0.07, P < 0.01/P < 0.05) and LDL-C (1.42 ± 0.07/1.47 ± 0.12 vs 1.72 ± 0.20, P < 0.01/P < 0.01) in hyperlipidemic mice significantly decreased. In addition, TC, HDL-C, AI, and LDL-C/HDL-C ratio were all positively changed. Meanwhile, the treatment markedly alleviated hepatic steatosis and significantly stimulated Nrf2 expression (73.79 ± 0.80/72.96 ± 1.22 vs 54.94 ± 1.84, P < 0.01/P < 0.01) in hepatocytes of hyperlipidemic mice. CONCLUSION: L. plantarum CAI6 and L. plantarum SC4 may protect against cardiovascular disease by lipid metabolism regulation and Nrf2-induced antioxidative defense in hyperlipidemic mice.

[Spatiotemporal variations of vegetation cover in Zhejiang Province and their relations to eco-climatic indices].

This paper studied the spatiotemporal variations of normalized difference vegetation index (NDVI) in Zhejiang Province in 1982-2006, and their relations to the dominant eco-climatic factors in the Province. In the study period, the vegetation cover in the Province had a slowly decreasing trend, and the area with a significant decrease of NDVI occupied 30.71% of the total. There were significant relationships between the eco-climatic indices and the NDVI of the following year. The NDVI was significantly positively correlated with biological aridity/humidity index, and significantly negatively correlated with biological warmth index, suggesting that the increase of humidity could promote vegetation growth, while excessive heat could inhibit the vegetation growth in the study area.

Anti-tumor activity of polysaccharides isolated from Patrinia scabra Bunge on U14 cervical carcinoma bearing mice.

The aim of our study was to investigate the effect of Patrinia scabra Bunge polysaccharide (PSB-P2) on cervical cancer cell (U14)-bearing mice. The tumor weight of mice treated with PSB-P2 (40, 80 mg/kg b.w.) was significantly lower than that of the control group and serum lactate dehydrogenase (LDH) activity was decreased, while serum alkaline phosphatase (AKP) level was only changed slightly. Meanwhile, the number of apoptotic tumor cells was significantly increased in the mice by the treatment of PSB-P2 (40, 80 mg/kg b.w.). At the same time, cell cycle analysis showed the accumulation of tumor cells in the G0/G1 phase and a relative decrease in the S phase. On the other hand, using the reverse transcription-polymerase chain reaction (RT-PCR) assay, PSB-P2 (40, 80 mg/kg b.w.) showed the up-regulation of p53 and Bax, and significant inhibition of Bcl-2 in tumor tissues. It suggests a possible mechanism of the inhibitory effect of PSB-P2 on tumor growth.

[Pith decompression of the femoral head and allograft fibula grafting for treatment of avascular necrosis of femoral head].

OBJECTIVE: To investigate the clinical efficacy of the pith decompression of the femoral head and fibular allograft transplantation in the treatment of early stage avascular necrosis. METHODS: From January 2004 to November 2008, 32 hips of 25 patients with avascular necrosis of femoral head of Ia-IIIb period were treated by the pith decompression of the femoral head and fibular allograft transplantation, hollow lag screw fixation, included 17 males and 8 females, aged from 20 to 55 years old (39.1 years on average). Preoperative pain was from 2 to 14 months (means 5.5 months). All patients were applied on conventional X-ray films, MRI examination, Harris score. RESULTS: The patients were followed up for 12 to 48 months (means 36.4 months). X-ray film showed 21 hips of 18 cases improved,6 hips of 4 cases unchanged, no collapse of articular surface, 3 hips of 2 cases deterioration, 2 hips of 1 case failed. Preoperative Harris score was (77.0 +/- 8.0) and postoperative (90.6 +/- 2.5), there was a significant difference (t = 1.67, P < 0.05). CONCLUSION: Pith decompression of the femoral head and fibular allograft transplantation in the treatment of early stage avascular necrosis of femoral head has advantage of joint function in bed-ridden after a short time, quick recovery,clinical symptoms improved. Its short-term efficacy is certain but long-term efficacy is still need further observation.

[Micro-modified Fulkerson osteotomy for the treatment of habituation patellar dislocation].

OBJECTIVE: To evaluate clinical effect of micro-modified Fulkerson osteotomy under arthroscope in treating habituation patellar dislocation. METHODS: Twenty patients of habituation patellar dislocation (25 knees) were treated by the medial retinaculum plication, lateral retinaculum releasing and modified Fulkerson osteotomy (tibial tubercle anteromedial transfer) under arthroscope. There were 5 males and 15 females with the age from 16- to 28-years-old (average of 21 years). The subjective symptoms and the joint function were evaluated according to Lysholm and Tegner scoring system. RESULTS: All the patients were followed up from 12 to 36 months with an average of 24 months. No found redislocation in the patients. The Lysholm score was 54.4 +/- 12.1 and 87.7 +/- 9.6 (t=2.33, P<0.05) before and after surgery respectively. The Tegner score was 2.8 +/- 0.8 and 5.1 +/- 1.3 (t=4.36, P<0.01) before and after surgery respectively. CONCLUSION: Micro-modified Fulkerson osteotomy under arthroscope for the treatment of habituation patellar dislocation is a rescheduled in extend knee equipment, its advantages including affirmative effect, minor damage, quick rehabilitation, fewer complications and lower rate of recurrence after operation.

Antitumor and immunomodulating effects of polysaccharides isolated from Solanum nigrum Linne.

We have examined the effects of the crude polysaccharides isolated from Solanum nigrum Linne (SNL-P) in vitro and in vivo against U14 cervical cancer. SNL-P showed no antiproliferative effects in vitro at a dose up to 1 mg/ml. In vivo administration with SNL-P (90, 180, 360 mg/kg b.w., p.o.) decreased the number of ascites tumor cells and prolonged the survival time of U14 cervical-cancer-bearing mice. FACScan flow cytometer analysis showed that most of the ascites tumor cells were arrested in G2/M phase of cell cycle and the ratio of CD4+/CD8+ peripheral blood T-lymphocyte subpopulations were restored following treatment of SNL-P. Furthermore, the treatment with SNL-P also caused a significant increment in IFN-gamma (p < 0.01, 90, 180 and 360 mg/kg b.w.) and a remarkable decrease in Il-4 (p < 0.01, 90, 180 mg/kg b.w.; p < 0.05, 360 mg/kg b.w.) by the method of ELISA. These data showed that SNL-P possess potent antitumor activity and SNL-P might exert antitumor activity via activation of different immune responses in the host rather than by directly attacking cancer cells on the U14 cervical cancer bearing mice. Thus, SNL-P could be used as an immunomodulator and an anticancer agent.

Antitumor effects of total alkaloids isolated from Solanum nigrum in vitro and in vivo.

This study demonstrated that the total alkaloids isolated from the traditional Chinese medicinal herb Solanum nigrum Linne (SNL-A) inhibited the growth of human cervical cancer HeLa cells in culture medium with much lower toxicity to human normal lymphocytes. By means of HE staining and TUNEL assay, our results further revealed that SNL-A induced cell death by apoptosis. An immunohistochemical assay showed down-regulation of the bcl-2 and p53 genes and no obvious change of bax gene in the SNL-A treated cells. Subcutaneous injection of HeLa cells induced tumor formation in nude mice, and SNL-A showed a significant inhibitory effect on tumor formation. These results suggested that SNL-A may be a potential, natural apoptosis-inducing agent for cervical cancer.

High-level expression of recombinant human nerve growth factor beta in milk of nontransgenic rabbits.

The technology for the large-scale production of therapeutic recombinant proteins remains a challenge in the biopharmaceutical industry. In this study, we reported a nontransgenic approach to producing a large quantity of human nerve growth factor beta (hNGF-beta) in rabbit milk by employing a recombinant adenoviral expression system. After directly instilling hNGF-beta recombinant adenoviruses into rabbit mammary glands, a polypeptide with a molecular weight of 13.2 kDa was detected in rabbit milk. The maximal expression level of hNGF-beta reached 346 mug/ml. The biological activity of recombinant hNGF-beta was confirmed using PC12 cells and cultures of dorsal root ganglion neurons from chicken embryos. Our data suggest that instilling recombinant adenovirus directly into the mammary gland of mammals is an efficient approach to producing a large quantity of hNGF-beta.

[Effects of rice-duck farming on paddy field's methane emission].

By using closed-chamber technique, the characteristics of CH4 emission from an integrated rice-duck ecosystem were studied in 2006 and 2007. The results showed that comparing with conventional flooded rice ecosystem (CK), integrated rice-duck system (RD) was distinguished in its high dissolved oxygen (DO) in field surface water and significantly lower CH4 emission, due to the activities of duck. In 2006, the average CH4 emission flux and the total CH4 emission during the whole rice growth period of RD were 6.84 +/- 1.49 mg +/- m(-2) x h(-1) and 19.34 +/- 1.15 g x m(-2), being 32.7% and 26.3% lower than those of CK (10.17 +/- 1.25 mg x m(-2) x h(-1) and 26.25 +/- 2.17 g respectively; while in 2007, the values of the two test items of RD were 7.68 +/- 0.74 mg x m(-2) x h(-1) and 18.41 +/- 1.05 g x m(-2), being 19.0% and 19.3% lower than those of CK (9.53 +/- 0.40 mg x m(-2) x h(-1) and 22.81 +/- 0.75 g +/- m(-2)), respectively. The emission flux of CH4 had two peaks, being appeared at tillering and heading stages, respectively. The seasonal fluctuations of CH4 emission flux had significant positive correlations with soil temperature and soil dissolved organic carbon content (DOC), but no obvious correlation with soil total organic carbon.

High-level expression of human lactoferrin in the milk of goats by using replication-defective adenoviral vectors.

The expression of human lactoferrin in the mammary gland is an attractive approach to diminish its current production cost. Previous attempts to produce lactorferrin in the milk of transgenic animals resulted in very high cost and uncertain results. In this paper, we have directly infused replication-defective adenovirus encoding human lactoferrin cDNA into the mammary gland of goats via the teat canal. In this way, we obtained a high level of expressed human lactoferrin up to 2g/L in the milk of goats. The milk serum was collected from the infected mammary gland 48 h post-infection and subjected to a 10% SDS-PAGE and Western blotting. A approximately 80-kDa protein was visualized after viral vector infection. Our results demonstrate that intraductal injection of recombinant replication-defective adenovirus vectors may provide a very useful tool for large-scale production of recombinant proteins of biopharmaceutical interest.