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1.  High-Purity Prostate Circulating Tumor Cell Isolation by a Polymer Nanofiber-Embedded Microchip for Whole Exome Sequencing 
PMCID: PMC3875622  PMID: 23529932
Electrospun nanomaterials; microfluidics; circulating tumor cell; whole exome sequencing; prostate cancer
2.  Radiation dose and survival of patients with stage IV non-small cell lung cancer undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy: reanalysis of the findings of a single-center prospective study 
BMC Cancer  2014;14:491.
The objective of this study was to evaluate the radiation dose and response in terms of local-regional progression-free survival (LRPFS) and overall survival (OS) of patients with stage IV non-small cell lung cancer (NSCLC) undergoing concurrent chemotherapy and thoracic three-dimensional radiotherapy.
In all, we enrolled 201 patients with stage IV NSCLC in this study and analyzed OS in 159 patients and LRPFS in 120.
The 1-, 2-, 3-, and 5-year OS rates were 46.2%, 19.5%, 11.7%, and 5.8%, respectively, the median survival time being 12 months. The median survival times in differential treatment response of primary tumors were 19 of complete response, 13 of partial response, 8 of stable disease, and 6 months of progressive disease, respectively (P = 0.000). The 1-, 2-, 3-, and 5-year LRPFS rates of patients undergoing four to five cycles with doses ≥63 Gy and <63 Gy were 77.4% and 32.6%, 36.2% and 21.7%, 27.2% and 0, and 15.9% and 0, respectively (P = 0.002). According to multivariate analyses, four to five cycles of chemotherapy, gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score stable or increased by at least 10 units were independent prognostic factors for better OS (P = 0.035, P = 0.008, and P = 0.000, respectively). Radiation dose to the primary tumor ≥63 Gy resulted in better OS (P = 0.057) and LRPFS (P = 0.051), both findings being of borderline significance.
Treatment of IV NSCLC with joint administration of four to five cycles of chemotherapy and three-dimensional radiotherapy may prolong survival, particularly in patients receiving ≥63 Gy radiotherapy, with gross tumor volume <175.00 cm3 and post-treatment Karnofsky Performance Status score not lower than pretreatment values.
PMCID: PMC4227092  PMID: 25001175
Non-small cell lung cancer; Stage IV; Concurrent chemoradiotherapy; Thoracic three-dimensional radiotherapy; Dose; Response
3.  Dryland Soil Hydrological Processes and Their Impacts on the Nitrogen Balance in a Soil-Maize System of a Freeze-Thawing Agricultural Area 
PLoS ONE  2014;9(7):e101282.
Understanding the fates of soil hydrological processes and nitrogen (N) is essential for optimizing the water and N in a dryland crop system with the goal of obtaining a maximum yield. Few investigations have addressed the dynamics of dryland N and its association with the soil hydrological process in a freeze-thawing agricultural area. With the daily monitoring of soil water content and acquisition rates at 15, 30, 60 and 90 cm depths, the soil hydrological process with the influence of rainfall was identified. The temporal-vertical soil water storage analysis indicated the local albic soil texture provided a stable soil water condition for maize growth with the rainfall as the only water source. Soil storage water averages at 0–20, 20–40 and 40–60 cm were observed to be 490.2, 593.8, and 358 m3 ha−1, respectively, during the growing season. The evapo-transpiration (ET), rainfall, and water loss analysis demonstrated that these factors increased in same temporal pattern and provided necessary water conditions for maize growth in a short period. The dry weight and N concentration of maize organs (root, leaf, stem, tassel, and grain) demonstrated the N accumulation increased to a peak in the maturity period and that grain had the most N. The maximum N accumulative rate reached about 500 mg m−2d−1 in leaves and grain. Over the entire growing season, the soil nitrate N decreased by amounts ranging from 48.9 kg N ha−1 to 65.3 kg N ha−1 over the 90 cm profile and the loss of ammonia-N ranged from 9.79 to 12.69 kg N ha−1. With soil water loss and N balance calculation, the N usage efficiency (NUE) over the 0–90 cm soil profile was 43%. The soil hydrological process due to special soil texture and the temporal features of rainfall determined the maize growth in the freeze-thawing agricultural area.
PMCID: PMC4085067  PMID: 25000400
4.  Prognosis of non-small cell lung cancer patients with bone oligometastases treated concurrently with thoracic three-dimensional radiotherapy and chemotherapy 
To evaluate the efficacy of three-dimensional radiotherapy for non-small cell lung cancer (NSCLC) patients with bone metastases.
Clinical data for 95 NSCLC patients with bone metastases were collected and prognostic factors were analyzed. All patients received radiation to their thoracic primary tumor and ≥2 cycles of chemotherapy.
Of these 95 patients, 47 patients had only bone metastases and 48 had both bone metastases and other organ metastases. Univariate analysis showed that factors that statistically significantly contributed to patients having longer overall survival (OS) included receiving a radiation dose to the primary tumor ≥63 Gy, responding to treatment and receiving ≥4 cycles of chemotherapy (p = 0.001, p = 0.037 and p = 0.009, respectively). A radiation dose to the primary tumor ≥63 Gy remained significant for patients with bone metastases only as well as those with bone and other organ metastases when they were analyzed separately (p = 0.045 and p = 0.012, respectively). For patients with bone metastases only, those with T1-2 tumors had longer OS than those with T3-4 (p = 0.048); and patients who received ≥4 cycles chemotherapy compared with those who received <4 cycles had similar OS (p = 0.385). On multivariate analysis, only a radiation dose ≥63 Gy (p = 0.028) and having only bone metastases (p = 0.006) were independent prognostic factors for better OS.
A radiation dose to the primary tumor ≥63 Gy and having only bone metastases were associated with better OS in NSCLC patients with bone metastases. For patients with bone metastases only, besides radiation dose, T status was also correlated with OS, whereas the number of chemotherapy cycles was not. Therefore, aggressive thoracic radiation may play an important role in improving OS.
PMCID: PMC4082286  PMID: 24962716
Non-small Cell Lung Cancer; Bone Metastases; Thoracic Radiotherapy; Chemotherapy
5.  Specific Capture and Release of Circulating Tumor Cells Using Aptamer Modified Nanosubstrates 
PMCID: PMC3786685  PMID: 23495071
Cancer Diagnosis; Circulating Tumor Cells; Nanostructured materials; Aptamer; Cell Capture; Cell Release
6.  Polymer Nanofiber-Embedded Microchips for Detection, Isolation, and Molecular Analysis of Single Circulating Melanoma Cells** 
Angewandte Chemie (International ed. in English)  2013;52(12):10.1002/anie.201208452.
PMCID: PMC3807678  PMID: 23436302
Circulating Tumor Cells; Single-Cell Analysis; Melanoma; BRAF Mutation; Cancer Diagnostics
7.  NanoVelcro Chip for CTC enumeration in prostate cancer patients 
Methods (San Diego, Calif.)  2013;64(2):10.1016/j.ymeth.2013.06.019.
Circulating tumor cells (CTCs) are one of the most crucial topics in rare cell biology and have become the focus of a significant and emerging area of cancer research. While CTC enumeration is a valid biomarker in prostate cancer, the current FDA-approved CTC technology is unable to detect CTCs in a large portion of late stage prostate cancer patients. Here we introduce the NanoVelcro CTC Chip, a device composed of a patterned silicon nanowire substrate (SiNW) and an overlaid polydimethylsiloxane (PDMS) chaotic mixer. Validated by two institutions participating in the study, the NanoVelcro Chip assay exhibits very consistent efficiency in CTC-capture from patient samples. The utilized protocol can be easily replicated at different facilities. We demonstrate the clinical utility of the NanoVelcro Chip by performing serial enumerations of CTCs in prostate cancer patients after undergoing systemic therapy. Changes in CTC numbers after 4–10 weeks of therapy were compared with their clinical responses. We observed a statistically significant reduction in CTCs counts in the clinical responders. We performed long-term follow up with serial CTC collection and enumeration in one patient observing variations in counts correlating with treatment response. This study demonstrates the consistency of the NanoVelcro Chip assay over time for CTC enumeration and also shows that continuous monitoring of CTC numbers can be employed to follow responses to different treatments and monitor disease progression.
PMCID: PMC3834112  PMID: 23816790
Nanomaterials; microfluidics; circulating tumor cell; prostate cancer; diagnostics
8.  Overall survival and toxicities regarding thoracic three-dimensional radiotherapy with concurrent chemotherapy for stage IV non-small cell lung cancer: results of a prospective single-center study 
BMC Cancer  2013;13:474.
The role of chemotherapy given concurrently with thoracic three-dimensional radiotherapy for stage IV non-small cell lung cancer (NSCLC) is not well defined. We performed this study to investigate overall survival and toxicity in patients with stage IV NSCLC treated with this modality.
From 2003 to 2010, 201 patients were enrolled in this study. All patients received chemotherapy with concurrent thoracic three-dimensional radiotherapy. The study endpoints were the assessment of overall survival (OS) and acute toxicity.
For all patients, the median survival time (MST) was 10.0 months, and the 1-, 2- and 3-year OS rates were 40.2%, 16.4%, and 9.6%, respectively. The MST was 14.0 months for patients who received a total radiation dose ≥63 Gy to the primary tumor, whereas it was 8.0 months for patients who received a total dose <63 Gy (P = 0.000). On multivariate analysis, a total dose ≥63 Gy, a single site of metastatic disease, and undergoing ≥4 cycles of chemotherapy were independent prognostic factors for better OS (P = 0.007, P = 0.014, and P = 0.038, respectively); radiotherapy involving metastatic sites was a marginally significant prognostic factor (P = 0.063). When the whole group was subdivided into patients with metastasis at a single site and multiple sites, a higher radiation dose to the primary tumor remained a significant prognostic factor for improved OS. For patients who received ≥4 cycles of chemotherapy, high radiation dose remained of benefit for OS (P = 0.001). Moreover, for the subgroup that received <4 chemotherapy cycles, the radiation dose was of marginal statistical significance regarding OS (P = 0.063). Treatment-related toxicity was found to be acceptable.
Radiation dose to primary tumor, the number of metastatic sites, and the number of chemotherapy cycles were independent prognostic factors for OS in stage IV NSCLC patients treated with concurrent chemoradiotherapy. In addition to systemic chemotherapy, aggressive thoracic radiotherapy was shown to play an important role in improving OS.
Trial registration
Registered on (ChiCTR-TNC-10001026)
PMCID: PMC3852781  PMID: 24118842
Non-small cell lung cancer; Stage IV; Concurrent chemoradiotherapy; Thoracic three-dimensional radiotherapy; Overall survival
9.  Higher Fish Intake Is Associated with a Lower Risk of Hip Fractures in Chinese Men and Women: A Matched Case-Control Study 
PLoS ONE  2013;8(2):e56849.
Fish is rich in nutrients that are favorable to bone health, but limited data are available regarding the relationship between fish intake and hip fractures. Our study examined the association between habitual fish intake and risk of hip fractures.
A case-control study was performed between June 2009 and June 2012 in Guangdong Province, China. Five hundred and eighty-one hip fracture incident cases, aged 55 to 80 years (mean: 71 years), were enrolled from four hospitals. 1∶1 matched controls by gender and age (±3 years) were also recruited from communities and hospitals. Face-to-face interviews were used to obtain habitual dietary intake and information on various covariates.
Univariate conditional logistic regression analyses showed significantly dose-dependent inverse correlations between the risk of hip fractures and the intake of fresh-water fish, sea fish, mollusca, shellfish, and total fish in all of the subjects (p-trend: <0.001–0.016). After adjusting for covariates, the associations were slightly attenuated but remained significant for all (p-trend: <0.001–0.017) except for fresh-water fish (p = 0.553). The ORs (95%CI) of hip fractures for the highest (vs. lowest) quartile were 0.80 (0.48–1.31) for fresh-water fish, 0.31 (0.18–0.52) for sea fish, 0.55 (0.34–0.88) for mollusca and shellfish, and 0.47 (0.28–0.79) for total fish, respectively. Stratified and interaction analyses showed that the association was more significant in males than in females (p-interaction = 0.052).
Higher intake of seafood is independently associated with lower risk of hip fractures in elderly Chinese. Increasing consumption of sea fish may benefit the prevention of hip fractures in this population.
PMCID: PMC3577656  PMID: 23437256
10.  Effects of the Nature and Concentration of Salt on the Interaction of the HIV-1 Nucleocapsid Protein with SL3 RNA§ 
Biochemistry  2010;49(17):3525-3533.
The mature nucleocapsid protein of HIV-1, NCp7, and the NC-domains in gag-precursors are attractive targets for anti-AIDS drug discovery. The stability of the 1:1 complex of NCp7 with a 20mer mimic of stem-loop 3 RNA (SL3, also called psi-RNA, in the packaging domain of genomic RNA) is strongly affected by changes in ionic strength. NC-domains recognize and specifically package genomic HIV-1 RNA, while electrostatic attractions and high concentrations of protein and RNA drive NCp7 to completely coat the RNA in the mature virion. The specific interactions from NCp7-binding to loop bases of SL3 produce 1:1 complexes in solutions that have [NaCl] at or above 0.2 M, while the electrostatic interactions can dominate at and below 0.15 M NaCl, leading to complexes that have mainly 1:2 RNA:protein. Persistent, non-equilibrium mixtures of 1:1 and protein-excess complexes can exist at these lower salt concentrations, where the distribution of complexes depends on the order of addition of RNA and protein. Adding salt causes rapid rearrangement of metastable multi-protein complexes to 1:1. The stability of complexes is also affected by the nature of the added salt, with 0.018 M MgCl2 and 0.200 M added NaCl producing the same Kd (21 ± 2 nM); acetate ion stabilizes the 1:1 complex by more than a factor of two compared to the same concentration of chloride ion. Maintaining a salt concentration of 0.2 M NaCl or 18 mM MgCl2 is sufficient for experiments to distinguish drug candidates that disrupt the specific SL3-NCp7 interactions in the 1:1 complex.
PMCID: PMC2872994  PMID: 20359247
RNA; HIV-1; nucleocapsid protein; fluorescence
11.  Isoflurane Inhibits the Tetrodotoxin-resistant Voltagegated Sodium Channel Nav1.8 
Anesthesiology  2009;111(3):591-599.
Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant (TTX-r) compared to other isoforms. Nav1.8 is highly expressed in dorsal root ganglion neurons and is functionally linked to nociception, but the sensitivity of TTX-r isoforms to inhaled anesthetics is unclear.
The sensitivities of heterologously expressed rat TTX-r Nav1.8 and endogenous tetrodotoxin-sensitive (TTX-s) Nav to the prototypic inhaled anesthetic isoflurane were tested in mammalian ND7/23 cells using patch-clamp electrophysiology.
From a holding potential of −70 mV, isoflurane (0.53±0.06 mM, ~1.8 MAC at 24°C) reduced normalized peak Na+ current (INa) of Nav1.8 to 0.55±0.03 and of endogenous TTX-s Nav to 0.56±0.06. Isoflurane minimally inhibited INa from a holding potential of −140 mV. Isoflurane did not affect voltage-dependence of activation, but significantly shifted voltage-dependence of steady-state inactivation by −6 mV for Nav1.8 and by −7 mV for TTX-s Nav. IC50 values for inhibition of peak INa were 0.67±0.06 mM for Nav1.8 and 0.66±0.09 mM for TTX-s Nav; significant inhibition occurred at clinically relevant concentrations as low as 0.58 MAC. Isoflurane produced use-dependent block of Nav1.8; at a stimulation frequency of 10 Hz, 0.56±0.08 mM isoflurane reduced INa to 0.64±0.01 vs. 0.78±0.01 for control.
Isoflurane inhibited the tetrodotoxin-resistant isoform Nav1.8 with potency comparable to that for endogenous tetrodotoxin-sensitive Nav isoforms, indicating that sensitivity to inhaled anesthetics is conserved across diverse Nav family members. Block of Nav1.8 in dorsal root ganglion neurons could contribute to the effects of inhaled anesthetics on peripheral nociceptive mechanisms.
PMCID: PMC2756082  PMID: 19672182
12.  Comparative Effects of Halogenated Inhaled Anesthetics on Voltage-gated Na+ Channel Function 
Anesthesiology  2009;110(3):582-590.
Inhibition of voltage-gated Na+ channels (Nav) is implicated in the synaptic actions of volatile anesthetics. We studied the effects of the major halogenated inhaled anesthetics (halothane, isoflurane, sevoflurane, enflurane and desflurane) on Nav1.4, a well characterized pharmacological model for Nav effects.
Na+ currents (INa) from rat Nav1.4 α-subunits heterologously expressed in Chinese hamster ovary cells were analyzed by whole cell voltage-clamp electrophysiological recording.
Halogenated inhaled anesthetics reversibly inhibited Nav1.4 in a concentration- and voltage-dependent manner at clinical concentrations. At equi-anesthetic concentrations, peak INa was inhibited with a rank order of desflurane > halothane ≈ enflurane > isoflurane ≈ sevoflurane from a physiological holding potential (−80 mV). This suggests that the contribution of Na+ channel block to anesthesia might vary in an agent-specific manner. From a hyperpolarized holding potential that minimizes inactivation (−120 mV), peak INa was inhibited with a rank order of potency for tonic inhibition of peak INa of halothane > isoflurane ≈ sevoflurane > enflurane > desflurane. Desflurane produced the largest negative shift in voltage-dependence of fast inactivation consistent with its more prominent voltage-dependent effects. A comparison between isoflurane and halothane showed that halothane produced greater facilitation of current decay, slowing of recovery from fast inactivation, and use-dependent block than isoflurane.
Five halogenated inhaled anesthetics all inhibit a voltage-gated Na+ channel by voltage- and use-dependent mechanisms. Agent-specific differences in efficacy for Na+ channel inhibition due to differential state-dependent mechanisms creates pharmacologic diversity that could underlie subtle differences in anesthetic and nonanesthetic actions.
PMCID: PMC2699670  PMID: 19225394
13.  Microencapsulated Genetically Engineered Lactobacillus plantarum 80 (pCBH1) for Bile Acid Deconjugation and Its Implication in Lowering Cholesterol 
Cholesterol is known to be a major risk factor for coronary heart disease (CHD). Current treatments for elevated blood cholesterol include dietary management, regular exercise, and drug therapy with fibrates, bile acid sequestrants, and statins. Such therapies, however, are often suboptimal and carry a risk for serious side effects. This study shows that microencapsulated Lactobacillus plantarum 80 (pCBH1) cells can efficiently break down and remove bile acids, and establishes a basis for their use in lowering blood serum cholesterol. Results show that microencapsulated LP80 (pCBH1) is able to effectively break down the conjugated bile acids glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) with bile salt hydrolase (BSH) activities of 0.19 and 0.08 μmol DCA/mg CDW/h respectively. This article also summarizes the physiological interrelationship between bile acids and cholesterol and predicts the oral doses of microencapsulated Lactobacillus plantarum 80 (pCBH1) cells required for lowering cholesterol.
PMCID: PMC545656  PMID: 15123889

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