Establishing and Externally Validating a Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score-Based Nomogram for Predicting Early Recurrence in BCLC Stage 0/A Hepatocellular Carcinoma Patients After Radical Liver Resection: A Multi-Center Study.

Purpose: Early recurrence (ER) is associated with poor prognosis in hepatocellular carcinoma (HCC). In this study, we developed and externally validated a nomogram based on the hemoglobin, albumin, lymphocytes, and platelets (HALP) score to predict ER for patients with BCLC stage 0/A HCC who underwent radical liver resection. Patients and Methods: A total of 808 BCLC stage 0/A HCC patients from six hospitals were included in this study, and they were assigned to a training cohort (n = 500) and an external validation cohort (n = 308). We used univariate and multivariate Cox regression analysis to identify the independent risk factors for disease-free survival (DFS). We also established and externally validated a nomogram based on these risk predictors. The nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), the calibration curve, decision curve analysis (DCA), and Kaplan‒Meier analysis. Results: Multivariate COX regression showed that HBV DNA ≥10,000 IU/mL (P < 0.001), HALP score ≤38.20 (P < 0.001), tumor size (P = 0.003), clinically significant portal hypertension (P = 0.001), Edmondson-Steiner grade (III-IV) (P = 0.007), satellite nodules (P < 0.001), and MVI (P = 0.001) were independent risk factors for post-operative tumor recurrence. The AUC of our nomogram for predicting the 2-year and 5-year DFS was 0.756 and 0.750, respectively, in the training cohort and 0.764 and 0.705, respectively, in the external validation cohort. We divided the patients into low-, intermediate- and high-risk groups according to the risk score calculated by the nomogram. There were statistically significant differences in the DFS and overall survival (OS) among the three groups of patients (P < 0.001). Conclusion: We developed and externally validated a new nomogram, which is accurate and can predict ER in BCLC stage 0/A HCC patients after curative liver resection.

Elevated SLC40A1 impairs cardiac function and exacerbates mitochondrial dysfunction, oxidative stress, and apoptosis in ischemic myocardia.

Iron homeostasis is crucial for optimal cardiac function. Iron deficiency and overload have been linked to the development of cardiomyopathy and heart failure (HF) via intricate mechanisms. Although the crucial role of SLC40A1 in iron metabolism by facilitating the efflux of cellular iron has been confirmed, its specific molecular functions in cardiovascular diseases remain poorly understood. In this study, we generated mice with inducible cardiomyocyte-specific overexpression of SLC40A1 for the first time. The overexpression of SLC40A1 in the cardiomyocytes of adult mice resulted in significant iron deficiency, leading to mitochondrial dysfunction, oxidative stress, and apoptosis, subsequently resulting in the development of fatal HF. Notably, SLC40A1 upregulation was observed in the ischemic region during the initial phase of myocardial infarction (MI), contributing to iron loss in the cardiomyocytes. Conversely, the cardiomyocyte-specific knockdown of SLC40A1 improved cardiac dysfunction after MI by enhancing mitochondrial function, suppressing oxidative stress, and reducing cardiomyocytes apoptosis. Mechanistically, Steap4 interacted with SLC40A1, facilitating SLC40A1-mediated iron efflux from cardiomyocytes. In short, our study presents evidence for the involvement of SLC40A1 in the regulation of myocardial iron levels and the therapeutic benefits of cardiomyocyte-specific knockdown of SLC40A1 in MI in mice.

Effective contribution ratio of the molar during sequential distalization using clear aligners and micro-implant anchorage: a finite element study.

INTRODUCTION: This study aims to investigate the biomechanical effects of anchorage reinforcement using clear aligners (CAs) with microimplants during molar distalization. And also explores potential clinical strategies for enhancing anchorage in the sequential distalization process. METHODS: Finite element models were established to simulate the CAs, microimplants, upper dentition, periodontal ligament (PDL), and alveolar bone. In group set I, the 2nd molars underwent a distal movement of 0.25 mm in group set II, the 1st molars were distalized by 0.25 mm after the 2nd molars had been placed to a target position. Each group set consisted of three models: Model A served as the control model, Model B simulated the use of microimplants attached to the aligner through precision cuts, and Model C simulated the use of microimplants attached by buttons. Models B and C were subjected to a series of traction forces. We analyzed the effective contribution ratios of molar distalization, PDL hydrostatic stress, and von Mises stress of alveolar bone. RESULTS: The distalization of the 2nd molars accounted for a mere 52.86% of the 0.25-mm step distance without any reinforcement of anchorage. The remaining percentage was attributed to the mesial movement of anchorage teeth and other undesired movements. Models B and C exhibited an increased effective contribution ratio of molar distalization and a decreased loss of anchorage. However, there was a slight increase in the undesired movement of molar tipping and rotation. In group set II, the 2nd molar displayed a phenomenon of mesial relapse due to the reciprocal force produced by the 1st molar distalization. Moreover, the efficacy of molar distalization in terms of contribution ratio was found to be positively correlated with the magnitude of force applied. In cases where stronger anchorage reinforcement is required, precision cuts is the superior method. CONCLUSIONS: The utilization of microimplants in conjunction with CAs can facilitate the effective contribution ratio of molar distalization. However, it is important to note that complete elimination of anchorage loss is not achievable. To mitigate undesired movement, careful planning of anchorage preparation and overcorrection is recommended.

Actual contribution ratio of maxillary and mandibular molars for total molar relationship correction during maxillary molar sequential distalization using clear aligners with Class II elastics: A finite element analysis.

INTRODUCTION: Class II elastics, in combination with clear aligners (CA), are efficient for molar distalization. However, the effects of this combination on intermaxillary molar relationship correction have yet to be investigated. This study aimed to investigate the actual contribution ratio of the maxillary and mandibular molars for total molar relationship correction during maxillary molar distalization using Class II elastics with CA and further explore therapeutic recommendations for clinical practice. METHODS: Finite element models (FEMs) were established, including the distalization of the second molars (Set I), followed by the distalization of the first molars (Set II). Model A simulated elastics attached by precision cutting, whereas Model B simulated elastics attached to buttons. Force magnitudes of 100 g, 150 g, and 200 g of force were applied. We recorded the contribution ratio of the maxillary and mandibular molars for total molar relationship correction, effective distalizing distance in 0.25 mm step distance, tipping and rotation angles, and the hydrostatic stress in the periodontal ligament. RESULTS: During maxillary molar distalization, mesialization of the mandibular molar had a notable contribution ratio for molar relationship correction. The mandibular first molar was mesialized with mesiolingual rotation tendency. Approximately half of the 0.25 mm step distance was occupied by maxillary molar distalization; the remainder was occupied by anchorage teeth mesialization and tipping or rotation. When traction forces increased, the total molar relationship correction and effective distalization increased; the mandibular molars mesialization contribution ratio also increased, as did rotation and inclination tendency. Precision cutting had a higher total molar relationship correction and more effective distalization than a button but also had a larger contribution ratio of mandibular molar mesialization and inclination or rotation. CONCLUSIONS: Mandibular molar mesialization should be considered when correcting the molar relationship using CA with intermaxillary elastics during maxillary molar distalization. It is also important to consider the anchorage teeth mesialization and undesired tipping or rotation.

LncRNA00638 promotes the osteogenic differentiation of periodontal mesenchymal stem cells from periodontitis patients under static mechanical strain.

BACKGROUND: The osteogenic differentiation capacity of periodontal mesenchymal stem cells (PDLSCs) can be influenced by different levels of static mechanical strain (SMS) in an inflammatory microenvironment. Long non-coding RNAs (lncRNAs) are involved in various physiological processes. However, the mechanisms by which lncRNAs regulate the osteogenic differentiation of PDLSCs remain unclear. METHODS: We investigated the responses of PDLSCs obtained from periodontitis patients and healthy people to 8% and 12%SMS. Gene microarray and bioinformatics analyses were implemented and identified lncRNA00638 as a target gene for the osteogenesis of PDLSCs from periodontitis patients under SMS. Competing endogenous RNA (ceRNA) network analysis was applied and predicted interactions among lncRNA00638, miRNA-424-5p, and fibroblast growth factor receptor 1 (FGFR1). Gene expression levels were regulated by lentiviral vectors. Cell Counting Kit-8 assays, alkaline phosphatase assays, and Alizarin Red S staining were used to examine the osteogenic potential. RT-qPCR and Western blot were performed to detect the expression levels of related genes and proteins. RESULTS: We found that 8% and 12% SMS exerted distinct effects on HPDLSCs and PPDLSCs, with 12% SMS having the most significant effect. By microarray analysis, we detected differentially expressed lncRNAs/mRNAs between 12% SMS strained and static PPDLSCs, among which lncRNA00638 was detected as a positive target gene to promote the osteogenic differentiation of PPDLSCs under SMS loading. Mechanistically, lncRNA00638 may act as a ceRNA for miR-424-5p to compete with FGFR1. In this process, lncRNA00638 and miR-424-5p suppress each other and form a network to regulate FGFR1. CONCLUSIONS: Our findings demonstrate that the lncRNA00638/miRNA-424-5p/FGFR1 regulatory network is actively involved in the regulation of PDLSC osteogenic differentiation from periodontitis patients under SMS loading, which may provide evidence for optimizing orthodontic treatments in patients with periodontitis.

Cognition's dependence on functional network integrity with age is conditional on structural network integrity.

Maintaining good cognitive function is crucial for well-being across the lifespan. We proposed that the degree of cognitive maintenance is determined by the functional interactions within and between large-scale brain networks. Such connectivity can be represented by the white matter architecture of structural brain networks that shape intrinsic neuronal activity into integrated and distributed functional networks. We explored how the function-structure connectivity convergence, and the divergence of functional connectivity from structural connectivity, contribute to the maintenance of cognitive function across the adult lifespan. Multivariate analyses were used to investigate the relationship between function-structure connectivity convergence and divergence with multivariate cognitive profiles, respectively. Cognitive function was increasingly dependent on function-structure connectivity convergence as age increased. The dependency of cognitive function on connectivity was particularly strong for high-order cortical networks and subcortical networks. The results suggest that brain functional network integrity sustains cognitive functions in old age, as a function of the integrity of the brain's structural connectivity.

Intercropping of Stylosanthes green manure could improve the organic nitrogen fractions in a coconut plantation with acid soil.

Intercropping green manure (GM) may be a good solution to the problems of acid soil in tropical plantations. Soil organic nitrogen (No) may change due to the application of GM. A three-year field experiment was conducted to determine the effect of different utilization patterns of Stylosanthes guianensis GM on soil No fractions in a coconut plantation. Three treatments were set: no GM intercropping (CK), intercropping and mulching utilization pattern (MUP), and intercropping and green manuring utilization pattern (GMUP). The content dynamics of soil total N (TN) and soil No fractions including of non-hydrolysable N (NHNo) and hydrolyzable N (HN) in the cultivated soil layer was examined. The results showed that after three years of intercropping, the TN content of the MUP and GMUP treatment was 29.4% and 58.1% respectively higher (P < 0.05) than those of the initial soil, and the No fractions content of GMUP and MUP treatment was 15.1%-60.0% and 32.7%-111.0% higher (P < 0.05) than those of the initial soil. The further results indicated that after three years of intercropping, compared with CK, GMUP and MUP could increase the content of TN by 32.6% and 61.7% respectively, and No fractions content was also increased by 15.2%-67.3% and 32.3%-120.3%% respectively (P < 0.05). The No fractions content of GMUP treatment was 10.3%-36.0% higher than those of MUP treatment (P < 0.05). These results indicated that intercropping Stylosanthes guianensis GM could significantly increase the soil N including of the TN an No fractions content, and the GMUP was more effective than MUP, therefore, GMUP is a better GM utilization pattern to improve the soil fertility and should be popularized in the tropical fruit plantation.

IPR treatment and attachments design in clear aligner therapy and risk of open gingival embrasures in adults.

BACKGROUND: The incidence of open gingival embrasures (OGE) in patients after fixed appliance treatment is relatively high, while there are no detailed reports on patients after clear aligner therapy. Also, no clinical studies with large sample size have investigated whether interproximal enamel reduction (IPR) can actually avoid OGE. The purpose of this study was to determine the prevalence of OGE in adults after clear aligner therapy and to investigate the risk of OGE associated with IPR treatment and attachment design, focusing on the amount and distribution in mandibular anterior teeth. METHODS: Pre-treatment and post-treatment intraoral frontal photographs of 225 non-extraction patients were evaluated retrospectively for the occurrence and severity of OGE. The amount of IPR and the number of attachments in the anterior teeth from subjects after screening were recorded according to the first version of clear aligner software (Clincheck, San Jose, USA) and clinical medical documents. Logistic regression analysis was performed to identify the factors contributing to OGE. RESULTS: The incidence of OGE in non-extraction patients after clear therapy between maxillary and mandibular central incisors was 25.7% and 40.3%, respectively. IPR was not associated with the occurrence of OGE but was associated with severity (P < 0.05). The number of attachments in the anterior teeth or central incisors was significantly related to the incidence of OGE (P < 0.05) but was not associated with severity. CONCLUSION: A high rate of OGE occurs after clear aligner therapy. Clinicians should be aware of the application of IPR and the design of attachments during clear aligner therapy.

Effects of upper-molar distalization using clear aligners in combination with Class II elastics: a three-dimensional finite element analysis.

INTRODUCTION: The effects of upper-molar distalization using clear aligners in combination with Class II elastics for anchorage reinforcement have not been fully investigated yet. The objective of this study is to analyze the movement and stress of the whole dentition and further explore guidelines for the selection of traction methods. METHODS: Three-dimensional (3D) finite element models are established to simulate the sequential molar distalization process, including the initial distalization of the 2nd molar (Set I) and the initial distalization of the 1st molar (Set II). Each group set features three models: a control model without Class II elastics (model A), Class II elastics attached to the tooth by buttons (model B), and Class II elastics attached to the aligner by precision cutting (model C). The 3D displacements, proclination angles, periodontal ligament (PDL) hydrostatic stress and alveolar bone von Mises stress in the anterior area are recorded. RESULTS: In all of the models, the maxillary anterior teeth are labial and mesial proclined, whereas the distal moving molars exhibit distal buccal inclination with an extrusion tendency. With the combination of Class II elastics, the anchorage was effectively reinforced; model C demonstrates superior anchorage reinforcement with lower stress distribution in comparison with model B. The upper canines in model B present an extrusion tendency. Meanwhile, the mandibular dentition in models B and C experience undesired movement tendencies with little discrepancy from each other. CONCLUSIONS: Class II elastics are generally effective for anchorage reinforcement as the upper-molar distalization is performed with clear aligners. Class II elastics attached to an aligner by precision cutting is a superior alternative for maxillary anchorage control in cases that the proclination of upper incisors and extrusion of upper canines are unwanted.

The three-dimensional displacement tendency of teeth depending on incisor torque compensation with clear aligners of different thicknesses in cases of extraction: a finite element study.

BACKGROUND: Despite the popularity of clear aligner treatment, the effect of the thickness of these aligners has not been fully investigated. The objective of this study was to assess the effects of incisor torque compensation with different thicknesses of clear aligner on the three-dimensional displacement tendency of teeth in cases of extraction. METHODS: Three-dimensional finite element models of the maxillary dentition with extracted first premolars, maxilla, periodontal ligaments, attachments, and aligners were constructed and subject to Finite Element Analysis (FEA). Two groups of models were created: (1) with 0.75 mm-thick aligners and (2) with 0.5 mm-thick aligners. A loading method was developed to simulate the action of clear aligners for the en masse retraction of the incisors. Power ridges of different heights were applied to both groups to mimic torque control, and the power ridges favoring the translation of the central incisors were selected. Then, we used ANSYS software to analyze the initial displacement of teeth and the principle stress on the PDL. RESULTS: Distal tipping, lingual tipping and extrusion of the incisors, distal tipping and extrusion of the canines, and mesial tipping and intrusion of the posterior teeth were all generated by clear aligner therapy. With the 0.5 mm-thick aligner, a power ridge of 0.7 mm could cause bodily retraction of the central incisors. With the 0.75 mm-thick aligner, a power ridge of 0.25 mm could cause translation of the central incisors. Aligner torque compensation created by the power ridges generated palatal root torque and intrusion of the incisors, intrusion of the canines, mesial tipping and the intrusion of the second premolar; these effects were more significant with a 0.75 mm-thick aligner. After torque compensation, the stress placed on the periodontal ligament of the incisors was distributed more evenly with the 0.75 mm-thick aligner. CONCLUSIONS: The torque compensation caused by power ridges can achieve incisor intrusion and palatal root torque. Appropriate torque compensation with thicker aligners should be designed to ensure bodily retraction of anterior teeth and minimize root resorption, although more attention should be paid to the anchorage control of posterior teeth in cases of extraction.

Multimodal fusion analysis of functional, cerebrovascular and structural neuroimaging in healthy aging subjects.

Brain aging is a complex process that requires a multimodal approach. Neuroimaging can provide insights into brain morphology, functional organization, and vascular dynamics. However, most neuroimaging studies of aging have focused on each imaging modality separately, limiting the understanding of interrelations between processes identified by different modalities and their relevance to cognitive decline in aging. Here, we used a data-driven multimodal approach, linked independent component analysis (ICA), to jointly analyze magnetic resonance imaging (MRI) of grey matter volume, cerebrovascular, and functional network topographies in relation to measures of fluid intelligence. Neuroimaging and cognitive data from the Cambridge Centre for Ageing and Neuroscience study were used, with healthy participants aged 18-88 years (main dataset n = 215 and secondary dataset n = 433). Using linked ICA, functional network activities were characterized in independent components but not captured in the same component as structural and cerebrovascular patterns. Split-sample (n = 108/107) and out-of-sample (n = 433) validation analyses using linked ICA were also performed. Global grey matter volume with regional cerebrovascular changes and the right frontoparietal network activity were correlated with age-related and individual differences in fluid intelligence. This study presents the insights from linked ICA to bring together measurements from multiple imaging modalities, with independent and additive information. We propose that integrating multiple neuroimaging modalities allows better characterization of brain pattern variability and changes associated with healthy aging.

Higher midlife CAIDE score is associated with increased brain atrophy in a cohort of cognitively healthy middle-aged individuals.

BACKGROUND: Structural brain changes associated with Alzheimer's disease (AD) can occur decades before the onset of symptoms. The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score has been suggested to be associated with accelerated brain atrophy in middle-aged subjects but the regional specificity of atrophic areas remains to be elucidated. METHODS: 3T T1-weighted magnetic resonance imaging scans of 160 cognitively healthy middle-aged participants (mean age = 52) in the PREVENT-Dementia cohort, from baseline and from follow-up after 2 years, were examined. Images were preprocessed using Computational Anatomy Toolbox 12. Voxel-based morphometry was performed in FSL 6.0.1 to identify areas of grey matter (GM) volume differences both cross-sectionally and longitudinally between subjects with high and low baseline CAIDE score (CAIDE score was dichotomized at cohort-median). A GM percentage of change map was created for each subject for evaluation of atrophy over 2 years. Analyses were adjusted for age, gender, education and total intracranial volume. RESULTS: Compared to subjects with CAIDE score ≤ 6 (low risk), subjects with CAIDE score > 6 (high risk) showed lower GM volume in the temporal, occipital, and fusiform cortex and lingual gyrus at baseline, and greater percentage of GM loss over 2 years in the supramarginal gyrus, angular gyrus, precuneus, lateral occipital cortex, superior parietal lobule and cingulate gyrus (corrected P < 0.05). CONCLUSION: This study demonstrated accelerated GM atrophy concentrated in several AD signature cortical regions in healthy middle-aged subjects with high CAIDE scores.

Osteogenic inducer sustained-release system promotes the adhesion, proliferation, and differentiation of osteoblasts on titanium surface.

OBJECTIVE: Biomaterial can be locally applied to promote the osseointegration of dental implants. This study aimed to fabricate an osteogenic inducer (OI) sustained-release system and to evaluate its effects on the adhesion, proliferation, and differentiation of osteoblasts on titanium surfaces. METHODS: First of all, different contents of OI solution were added to the poly (lactic-co-glycolic acid) (PLGA) gel individually to investigate the best physical properties and drug-release rate. Moreover, osteoblasts were isolated from the calvaria of two-month-old New Zealand rabbits through sequential enzymatic digestion. Osteoblasts were seeded onto the surface of Ti disks (control group), Ti coated with PLGA gel (PLGA group), and Ti coated with the OI sustained-release system (PLGA+OI group). Cell adhesion was observed by scanning electron microscopy. Cell proliferation was analyzed by cell counting kit-8. Cell differentiation was tested by alizarin red staining, alkaline phosphatase (ALP) activity and osteogenic-related gene expression. RESULTS: The OI sustained-release system contained 15% OI solution had appropriate physical properties and drug-release rate. The osteoblasts in the PLGA+OI group were in a typical spindle shape with a considerable number indicating the promotion of adhesion and proliferation. The expression of early and late stage osteoblast differentiation genes in the PLGA+OI group were significantly higher than that of the control group and PLGA group at each time point. The PLGA group showed accelerated adhesion and differentiation but reduced proliferation compared with the control. CONCLUSION: The OI sustained-release system promotes the adhesion, proliferation, and differentiation of osteoblasts on titanium surfaces. This system is a cost-effective osteoconductive biomaterial that might be promising for use in dental implantation.

HO-1 induced autophagy protects against IL-1 ß-mediated apoptosis in human nucleus pulposus cells by inhibiting NF-κB.

In this study, we investigated the role of heme oxygenase-1 (HO-1) in intervertebral disc degeneration (IDD) by assessing the effects of HO-1 overexpression on IL-1ß-induced apoptosis in nucleus pulposus cells (NPCs). Immunohistochemical staining showed HO-1 expression to be lower in NPCs from IDD patients than from patients with lumbar vertebral fractures (LVF). Western blot analysis showed HO-1 and LC3-II/I levels to be lower in NP tissues from IDD patients than from LVF patients, suggesting suppression of autophagy in degenerative intervertebral disc. Consistent with that idea, autophagy was increased in HO-1-overexpressing NPCs while IL-1ß-induced apoptosis was reduced. These effects were reversed by treatment with the early autophagy inhibitor 3-methyl adenine, which suggests HO-1-induced autophagy suppresses IL-1ß-induced apoptosis in NPCs. HO-1 overexpression promoted autophagy by increasing levels of Beclin-1/PI3KC3 complex. Phospho-P65 levels were lower in HO-1-overexpressing NPCs, suggesting inhibition of NF-κB-mediated apoptosis. Our study thus demonstrates that HO-1 promotes autophagy by enhancing formation of Beclin-1/PI3KC3 complex and suppresses IL-1ß-induced apoptosis by inhibiting NF-κB. We suggest that HO-1 is a potential therapeutic target to alleviate IDD.

[Effects of flavonoids from Pyrrosiae folium on pathological changes and inflammatory response of diabetic nephropathy].

Diabetic nephropathy (DN) is closely related to immune-mediated inflammatory damage. Pyrrosiae folium is used commonly for the urinary system diseases with a good efficacy, which contains abundant flavonoids (SWHT). This study was performed to investigate the therapeutic effect of SWHT on DN and its effect on inflammatory response. In this study, the main active components of SWHT were identified by high performance liquid chromatography (HPLC). The results showed that SWHT mainly contained mangiferin and isomucoside. Rat model of diabetic nephropathy (DN) was established by feeding high glucose & high fat diet and injecting streptozocin (STZ). Then the rats were randomly divided into control group, DN model group, positive control group, and SWHT groups (50, 100, 200 mg·kg⁻¹, ig). The levels of AGEs and RAGE in serum were measured by ELISA after 12 weeks of drug administration. The serum creatinine, blood urea nitrogen and total protein levels were detected by using test kit. HE staining and transmission electron microscopy were applied to observe the pathological changes and structure of renal tissue. Western blot and ELISA were used to detect the protein expression and content levels of interleukin 6 (IL-6), tumor necrosis factor (TNF-α) and IL-1ß in renal tissue. Results showed that SWHT significantly decreased serum AGEs and RAGE levels in DN rats; decreased serum creatinine, blood urea nitrogen and total urinary protein levels, improved renal pathological damages and reduced basement membrane thickening in DN rats. In addition, SWHT down-regulated the protein expression levels of inflammatory mediators IL-6, TNF-α and IL-1ß. The research studies indicated that SWHT component had a potential anti-diabetic nephropathy activity, and its improvement effect on pathological damages may be related to reducing inflammation. This provides the basis for the scientific and rational application of P. folium, and also provides active components for further development of Chinese medicine for diabetic nephropathy.

A Chinese herbal Formula, Chang-Wei-Qin, Synergistically Enhances Antitumor Effect of Oxaliplatin.

Chang-Wei-Qing (CWQ), a Chinese herbal formula, has long been employed clinically to treat cancers. In this study, we investigated the synergistic effect of CWQ with oxaliplatin (OXA) on the tumor growth inhibition of orthotopic transplanted colon cancer and explored the underlying mechanism. By generating the orthotopic transplanted nude mouse model of human colon carcinoma, we found that (1) CWQ enhanced OXA-mediated tumor suppression by 4.25-fold. (2) The body weights of nude mice in CWQ group and combination group were increased. (3) The survival time of tumor-bearing nude mice was dramatically improved in CWQ and CWQ/OXA group. (4) CWQ could restore OXA-mediated deregulation of copper transporter genes, hCTR1, ATP7A and ATP7B. (5) OXA-induced drug resistance index for OXA, 5-FU, HCPT and THP were 7.59, 4.28, 5.78 and 4.50 respectively, while the reversal index by combined CWQ treatment were 6.57, 2.61, 4.97 and 3.10, respectively. Our study demonstrates that the repeated intraperitoneal injection of OXA can induce multi-drug resistance of orthotopic transplanted nude mouse model of human colon carcinoma. The CWQ treatment can alleviate OXA-triggered side effects and reverse platinum drug resistance via up-regulation of hCTR1 expression and down-regulation of ATP7A and ATP7B levels.

Quantitative relationship between visibility and mass concentration of PM2.5 in Beijing.

The pollution of particulate matter less than 2.5 microm (PM2.5) is a serious environmental problem in Beijing. The annual average concentration of PM2.5 in 2001 from seasonal monitor results was more than 6 times that of the U.S. national ambient air quality standards proposed by U.S. EPA. The major contributors to mass of PM2.5 were organics, crustal elements and sulfate. The chemical composition of PM2.5 varied largely with season, but was similar at different monitor stations in the same season. The fine particles (PM2.5) cause atmospheric visibility deterioration through light extinction. The mass concentrations of PM2.5 were anti-correlated to the visibility, the best fits between atmospheric visibility and the mass concentrations of PM2.5 were somehow different: power in spring, exponential in summer, logarithmic in autumn, power or exponential in winter. As in each season the meteorological parameters such as air temperature and relative humidity change from day to day, probably the reason of above correlations between PM2.5 and visibility obtained at different seasons come from the differences in chemical compositions of PM2.5.

Chemical composition and quantitative relationship between meteorological condition and fine particles in Beijing.

The recent year's monitor results of Beijing indicated that the pollution level of fine particles PM2.5 showed an increasing trend. To understand pollution characteristics of PM2.5 and its relationship with the meteorological conditions in Beijing, a one-year monitoring of PM2.5 mass concentration and correspondent meteorological parameters was performed in Beijing in 2001. The PM2.5 levels in Beijing were very high, the annual average PM2.5 concentration in 2001 was 7 times of the National Ambient Air Quality Standards proposed by US EPA. The major chemical compositions were organics, sulfate, crustals and nitrate. It was found that the mass concentrations of PM2.5 were influenced by meteorological conditions. The correlation between the mass concentrations of PM2.5 and the relative humidity was found. And the correlation became closer at higher relative humidity. And the mass concentrations of PM2.5 were negtive-correlated to wind speeds, but the correlation between the mass concentration of PM2.5 and wind speed was not good at stronger wind.