[Predictive value of aMAP risk score for early recurrence of small hepatocellular carcinoma after microwave ablation].

Objective: To explore the value of the aMAP risk score (age, male, albumin-bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors. Results: Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group (P=0.001). Conclusions: The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..

[Study on the comparison of postoperative liver injury caused by hepatic arterial perfusion chemotherapy combined with targeted immunotherapy with hepatic arterial chemoembolization combined with targeted immunotherapy for intermediate-and advanced-stage liver cancer].

Objective: To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs). Methods: Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ(2) test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results: This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ(2)=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ(2)=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ(2)=20.298, P < 0.001, 54.9% vs. 85.7%, χ(2)=17.917, P < 0.001;40.2% vs. 55.8%, χ(2)=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ(2)=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion: The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.

Localization of CgVPE1 in secondary cell wall formation during tracheary element differentiation in the pericarp of Citrus grandis 'Tomentosa' fruits.

MAIN CONCLUSION: CgVPE1 is important in the differentiation of TE cells in C. grandis 'Tomentosa' fruits as it may directly affects secondary cell wall construction while participating in PCD. The vacuolar processing enzyme (VPE) plays an important role in both developmental and environmentally inducible programmed cell death (PCD); it was originally identified as a cysteine protease localized in the vacuole to activate and mature vacuolar proteins in plants. Interestingly, we found a VPE called CgVPE1 to be associated with deposition of the secondary cell wall in tracheary element (TE) cells in the pericarp of Citrus grandis 'Tomentosa' fruits. We then used ultrathin sections and the TUNEL assay to verify that PCD is involved in TE development. Furthermore, CgVPE1 was found to be mainly expressed in secretory cavities and TEs in the pericarp of Citrus grandis 'Tomentosa' fruits. Immunolocalization of CgVPE1 in the pericarp indicated that CgVPE1 is mainly distributed in the central large vacuole, endoplasmic reticulum, Golgi vesicles, cytosol, and secondary wall before TE maturation. CgVPE1 appeared earlier in the endoplasmic reticulum and Golgi vesicles of TEs cells. The vesicles containing CgVPE1 near the large central vacuole and secondary wall were observed, respectively. CgVPE1 proteins content in the cytoplasm decreased sharply, while the CgVPE1 content in the secondary cell wall did not change significantly after vacuole rupture. CgVPE1 protein contents in the secondary cell wall were significantly reduced until the TE cells developed into hollow thick-walled cells. Furthermore, labeling of VPE homologues in Arabidopsis thaliana using immunoelectron microscopy with anti-CgVPE1 antibody revealed that VPE homologues were specifically distributed in the secondary cell wall of stem TEs. Overall, these results suggested that CgVPE1 is not only involved PCD during TE cell development; furthermore, it may directly participate in the construction of plant secondary cell walls.

Effects of guanidinoacetic acid and coated folic acid supplementation on growth performance, nutrient digestion and hepatic gene expression in Angus bulls.

To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA-) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA- diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA- diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.

[Regulatory effect of molecular targeted drugs on the immune system for liver cancer].

Molecular targeted drugs are the first choice for systemic treatment of liver cancer. In the past decade, several anti-liver cancer targeted drugs have been launched. More recently, immunotherapy has become a dazzling nova in the field of systemic treatment of liver cancer. Nivolumab and pembrolizumab have been approved as second-line treatments for patients with advanced hepatocellular carcinoma treated with sorafenib. However, the effect of single-agent treatment is always unsatisfactory in advanced liver cancer. An increasing number of evidences suggests that molecular targeted drugs have important immunomodulatory effects for liver cancer, and several targeted combined immunotherapies have also shown promising clinical effectiveness. This paper reviews the immunomodulatory effects of several molecular targeted drugs in the field of liver cancer.

[Analysis of the effect of microwave ablation in the treatment of small liver cancer].

Objective: To explore the clinical effect of microwave ablation in the treatment of early small liver cancer (≤3 cm). Methods: 103 cases with small liver cancer (tumor number < 3 and maximum tumor diameter < 3 cm) who underwent microwave ablation from November 2016 to November 2018 were retrospectively collected. The rate of residual lesions, recurrence rate one-year after the operation, and surgical complications were observed and grouped according to tumor size (< 2 cm and≥2 cm group) and tumor numbers (solitary and 2 ~ 3 lesion groups). The therapeutic effects of each group were compared and analyzed. Results: The tumor residual rate and one-year recurrence rate of small liver cancer after microwave ablation were 11.7% and 35.0%, respectively. The post-ablation syndrome incidence rate was 52.4%, with no serious adverse events. Compared with tumors < 2 cm, patients with≥2 cm had a higher postoperative residual rate (χ(2) = 7.651, P = 0.006), and the one-year recurrence rate of more solitary nodular tumors was lower (χ(2) = 10.125, P = 0.001). Conclusion: Microwave ablation is a safe and effective treatment for early small liver cancer, and it is more effective for small solitary nodules (< 2 cm).

[Clinical efficacy and safety analysis of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma: a multicenter retrospective study].

Objective: To analyze the clinical efficacy and safety of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma (HCC). Methods: Ninety-four cases with mid-and advanced-stage HCC who received camrelizumab combined with apatinib as second-line treatment were enrolled. Routine blood test, blood biochemical indexes, tumor stage, tumor imaging characteristics, previous treatment strategies and other clinical data before treatment were documented. Imaging examination follow-up results and adverse reactions during treatment were followed up until the end of follow-up or loss of follow-up or death. Kaplan-Meier method was used to analyze the clinical efficacy. Results: As of the last follow-up, 94 cases with mid-and advanced-stage HCC had received camrelizumab combined with apatinib as second-line treatment. Among them, 15 cases were lost to follow-up, 31 cases died, and 48 cases survived. The overall remission rate was 31.9%. The overall disease control rate was 71.3%. The median time to disease-free progression was 6.6 months. The median time to disease progression was not yet available. The 1-year cumulative survival rate was 62.3%. Grade 3 and above adverse reactions mainly included were thrombocytopenia (7.4%), abdominal pain (4.3%), active hepatitis (4.3%), leukopenia (4.3%), diarrhea (3.2%), hand-foot syndrome (3.2%). All adverse reactions were effectively controlled. Conclusion: Camrelizumab combined with apatinib can effectively prolong the survival period of patients with mid-and advanced-stage HCC, and it is well tolerated.

Large-scale tissue-specific and temporal gene expression profiles in Pengze crucian carp.

In the present study, the tissue-specific and temporal gene expression profiles of four catalogues of gonadal development-related genes (sex differentiation-related, steroid receptor, steroidogenic, and structural genes) were detected in nine tissues and during 11 successive developmental stages in the Pengze crucian carp (Pcc) (a triploid mono-female gynogenic fish). The results showed that these target genes exhibited overlapping distributions in various tissues, with the exception of Pcc-vasa and Pcc-cyp17a1. Gene expression profiling of the developmental stages showed that all of the target genes simultaneously reached peak expression levels at 40 and 48 days post hatching (dph). Both 40 and 48 dph appeared to be two key time points associated with the process of Pcc gonadal development. These data will provide a clear understanding of gene expression patterns associated with the gonadal development-related genes of this gynogenic teleost.

Effect of polychlorinated biphenyls on oxidation stress in the liver of juvenile GIFT, Oreochromis niloticus.

The present study clearly showed that chronic exposure to polychlorinated biphenyls (PCBs) at environmentally relevant concentrations can damage juvenile tilapia livers by modulating antioxidant enzyme activities and gene transcription, which affects toxic bioaccumulation and histological congestion. The results suggest that PCBs caused a decrease in the activity of some hepatic antioxidative and biotransformation enzymes (SOD, CAT, GST, T-GSH, and MDA) in tilapia at 7 days, as well as transcriptional changes (sod, cat, and gst). Except for some antioxidant parameters (T-GSH, GSH/GSSG, T-AOC, and MDA), significant declines and increases occurred at 14 and 21 days, respectively. Most of the antioxidant enzymatic signatures and genotoxicity significantly increased at 14 and 21 days. This study presented evidence that PCBs could result in hepatic toxicity through oxidative stress in the early growth stages of tilapia, and we speculated that oxidative stress plays an important role in embryonic developmental toxicity induced by PCBs.

Prevalence and clinical distribution of multidrug-resistant bacteria (3537 isolates) in a tertiary Chinese hospital (January 2012-December 2013).

OBJECTIVE: Multidrug-resistant organisms (MDROs) have become a widespread serious problem in recent years. Our objective was to determine the prevalence and clinical distribution of MDROs in a tertiary care hospital in China from January 1, 2012 to December 31, 2013. METHODS: The strains were cultured according to standard methods; bacterial identification and susceptibility testing were detected by Vitek 2 system. The prevalence and clinical distribution of extended-spectrum ß-lactamases (ESBLs)-producing enterobacteriaceae, carbapenem-resistant enterobacteriaceae (CRE), multiple-drug/pan-drug resistant P. aeruginosa (MDR/PDR-PA), carbapenem-resistant A. baumannii (CR-AB), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococcus (VRE) were analyzed by WHONET 5.6. RESULTS: A total of 3537 (33.4%) MDROs were found among 10,594 microbial isolates. ESBLs producing E. coli (ESBLs-ECO) (1153 cases) were the most frequent MDROs, followed by CR-AB (827 cases). The proportion of acquired resistance of A. baumannii (48.9%) accounted for the highest in all the MDROs. These MDROs were mainly isolated from respiratory (70.3%) and secretions (12.7%). Various types of intensive care unit (ICU) and surgery were the main source departments. The proportion of CRE and VRE were relatively few. CRE was most isolated from respiratory tract and closed body cavity fluid, while the distribution of VRE was relatively dispersed. CONCLUSION: High prevalence of MDROs has emerged in our hospital, particular in various ICU and surgical department. The effective way to prevent the further spread of MDROs is to strengthen the protection of respiratory tract and surgical wounds.

PTEN hypermethylation profiles of Chinese Kazakh patients with esophageal squamous cell carcinoma.

Aberrant DNA methylation of promoter region CpG islands may serve as an alternative mechanism to genetic defects in the inactivation of tumor suppressor genes (TSGs) in human malignancies. The aim of this study was to examine the promoter methylation status of the PTEN TSG and its association with esophageal squamous cell carcinoma (ESCC) carcinogenesis in a Chinese Kazakh population, which is known to have a relatively high ESCC incidence and mortality. The methylation status of the PTEN promoter region was determined in patients with ESCC (n = 95) and healthy individuals (n = 65) using highly sensitive Sequenom Epityper assays. The methylation level of the PTEN gene was significantly higher in patients with ESCC than in healthy controls. The median methylation level was 10.0% (interquartile range [IQR]: 7.0-11.0%) in patients with ESCC and 6.0% in controls (IQR: 4.0-9.0%; P = 0.001). PTEN methylation levels were higher in male patients with ESCC than in male controls, whereas a trend toward significance was observed between female patients with ESCC and female controls (P = 0.005 and P = 0.086, respectively). The PTEN methylation level was associated with histopathological grade and lymph node metastasis in patients with ESCC (P = 0.002 and P = 0.009, respectively). To our knowledge, this is the first report to show the presence of PTEN promoter CpG hypermethylation in ESCC and its association with tumor metastasis.

Combination of intense pulsed light and fractional CO(2) laser treatments for patients with acne with inflammatory and scarring lesions.

BACKGROUND: Various laser and light sources are been used increasingly in cosmetic dermatology. AIM: To evaluate the efficacy and safety of combination intense pulsed light (IPL) and fractional CO2 laser in treating patients with acne with both inflammatory and scarring lesions. METHODS: In total, 37 Chinese patients with acne with facial inflammatory and scar lesions were treated. Successive sessions of 4-6 IPL treatments followed by 2 sessions of fractional CO2 laser treatments were applied. Effectiveness was determined by the dermatologist's evaluation, patient self-assessment, and devices that measure skin colour, sebum secretion and skin hydration. RESULTS: IPL treatments significantly reduced the inflammatory lesion score and the atrophic scar score compared with baseline. Subsequent fractional CO2 laser treatments further decreased the atrophic scar score. Both scores remained low when patients were followed up at 6 months. Around 90% of the patients experienced significant or moderate overall improvement, and almost 80% patients rated their results as 'excellent' or 'good'. The melanin index (MI), erythema index (EI) and skin sebum level all significantly decreased after IPL treatments, and the EI and sebum level were still low when assessed at the 3-month follow-up, although the MI had increased again. The adverse effects (AEs) of both treatments were transient and bearable. CONCLUSIONS: IPL in combination with fractional CO2 laser was effective in treating patients with acne with both inflammatory lesions and atrophic scars, and the AEs were acceptable.

Resveratrate protects human skin from damage due to repetitive ultraviolet irradiation.

BACKGROUND: Ultraviolet (UV) exposure results in the production reactive oxygen species. Resveratrol has attracted considerable attentions owing to its natural abundance and multiple biological effects. OBJECTIVE: To investigate the protective effects of resveratrate against damage to human skin induced by repetitive solar simulator ultraviolet radiation (ssUVR). MATERIALS AND METHODS: Fifteen healthy volunteers were enrolled, and six sites on the non-exposed dorsal skin of each volunteer were marked for study. Sites 1-4 were exposed to ssUVR at a dosage of 1.5 minimal erythema dose for consecutive 4 days. Immediately after each exposure, one test material (resveratrate + antioxidant, antioxidant, resveratrate, vehicle) was applied to one of the four sites. Site 5 and site 6 were marked as positive control site (UVR only) and baseline control site (no treatment, no UVR). L*a*b values were assessed preprocedure and postprocedure. Skin biopsies were taken 24 h after the last irradiation. The specimens were stained to determine the number of sunburn cells and melanin content melanin. RESULTS: On resveratrate treated sites, erythema was barely seen with only slight decrease of L value and insignificant increase of *a value. Furthermore, resveratrate significantly inhibited sunburn cell formation, and decreased Fontana-Masson staining in skin samples. CONCLUSIONS: Resveratrate exerts protective effects against repetitive ssUVR-induced sunburn and suntan.

Binding modes of GDP, GTP and GNP to NRAS deciphered by using Gaussian accelerated molecular dynamics simulations.

Probing binding modes of GDP, GTP and GNP to NRAS are of significance for understanding the regulation mechanism on the activity of RAS proteins. Four separate Gaussian accelerated molecular dynamics (GaMD) simulations were performed on the apo, GDP-, GTP- and GNP-bound NRAS. Dynamics analyses suggest that binding of three ligands highly affects conformational states of the switch domains from NRAS, which disturbs binding of NRAS to its effectors. The analyses of free energy landscapes (FELs) indicate that binding of GDP, GTP and GNP induces more energetic states of NRAS compared to the apo NRAS but the presence of GNP makes the switch domains more ordered than binding of GDP and GNP. The information of interaction networks of ligands with NRAS reveals that the π-π interaction of residue F28 and the salt bridge interactions of K16 and D119 with ligands stabilize binding of GDP, GTP and GNP to NRAS. Meanwhile magnesium ion plays a bridge role in interactions of ligands with NRAS, which is favourable for associations of GDP, GTP and GNP with NRAS. This work is expected to provide useful information for deeply understanding the function and activity of NRAS.

Development of a novel ArcCHECK(™) insert for routine quality assurance of VMAT delivery including dose calculation with inhomogeneities.

PURPOSE: To design a versatile, nonhomogeneous insert for the dose verification phantom ArcCHECK(™) (Sun Nuclear Corp., FL) and to demonstrate its usefulness for the verification of dose distributions in inhomogeneous media. As an example, we demonstrate it can be used clinically for routine quality assurance of two volumetric modulated arc therapy (VMAT) systems for lung stereotactic body radiation therapy (SBRT): SmartArc(®) (Pinnacle(3), Philips Radiation Oncology Systems, Fitchburg, WI) and RapidArc(®) (Eclipse(™), Varian Medical Systems, Palo Alto, CA). METHODS: The cylindrical detector array ArcCHECK(™) has a retractable homogeneous acrylic insert. In this work, we designed and manufactured a customized heterogeneous insert with densities that simulate soft tissue, lung, bone, and air. The insert offers several possible heterogeneity configurations and multiple locations for point dose measurements. SmartArc(®) and RapidArc(®) plans for lung SBRT were generated and copied to ArcCHECK(™) for each inhomogeneity configuration. Dose delivery was done on a Varian 2100 ix linac. The evaluation of dose distributions was based on gamma analysis of the diode measurements and point doses measurements at different positions near the inhomogeneities. RESULTS: The insert was successfully manufactured and tested with different measurements of VMAT plans. Dose distributions measured with the homogeneous insert showed gamma passing rates similar to our clinical results (∼99%) for both treatment-planning systems. Using nonhomogeneous inserts decreased the passing rates by up to 3.6% in the examples studied. Overall, SmartArc(®) plans showed better gamma passing rates for nonhomogeneous measurements. The discrepancy between calculated and measured point doses was increased up to 6.5% for the nonhomogeneous insert depending on the inhomogeneity configuration and measurement location. SmartArc(®) and RapidArc(®) plans had similar plan quality but RapidArc(®) plans had significantly higher monitor units (up to 70%). CONCLUSIONS: A versatile, nonhomogeneous insert was developed for ArcCHECK(™) for an easy and quick evaluation of dose calculations with nonhomogeneous media and for comparison of different treatment planning systems. The device was tested for SmartArc(®) and RapidArc(®) plans for lung SBRT, showing the uncertainties of dose calculations with inhomogeneities. The new insert combines the convenience of the ArcCHECK(™) and the possibility of assessing dose distributions in inhomogeneous media.

Effect of soy isoflavones on blood pressure: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: The effect of soy isoflavones on blood pressure is controversial. The objective of this study was to evaluate the effect of dietary soy isoflavones on blood pressure. METHODS AND RESULTS: Trials were searched in PubMed, the Cochrane Library, Embase and references cited in related reviews and studies. A total of eleven trials were reviewed. Meta-analysis results showed a mean decrease of 2.5 mm Hg (95% CIs, - 5.35 to 0.34 mm Hg; P = 0.08) for systolic blood pressure and 1.5 mm Hg (95% CIs, - 3.09 to 0.17 mm Hg; P = 0.08) for diastolic blood pressure in the soy isoflavones-treated group compared to placebo. Meta-regression and subgroup analyses indicated that blood pressure status was a significant predictor of heterogeneity for the effect of soy isoflavones on blood pressure. Subgroup analysis of hypertensive subjects revealed that a greater blood pressure reduction was identified in the soy isoflavone-treated group compared to placebo (5 trials; SBP: - 5.94, 95% CIs [- 10.55, - 1.34] mm Hg, P = 0.01; DBP: - 3.35, 95% CIs [- 6.52, - 0.19] mm Hg, P = 0.04). In contrast, treatment with soy isoflavones did not lead to a significant reduction in blood pressure in normotensive subjects (6 trials; SBP: 0.29, 95% CIs [- 2.39, 2.97] mm Hg, P = 0.83; DBP: - 0.43, 95% CIs [- 1.66, 0.81] mm Hg, P = 0.50). CONCLUSION: Soy isoflavones had an effect of lowering blood pressure in hypertensive subjects, but not in normotensive subjects. Larger trials need to be carried out to confirm the present findings.

Meta-analysis demonstrates association between Arg72Pro polymorphism in the P53 gene and susceptibility to keloids in the Chinese population.

Although there is evidence suggesting genetic susceptibility for keloids, studies investigating the association between Arg72Pro polymorphism in the P53 gene and tendency to form keloids have given variable results. We made a meta-analysis of the effects of P53 Arg72Pro polymorphism on keloid risk in the Chinese population by conducting searches of the published literature in Pubmed, Embase, CBMdisc, and CNKI databases up to June 2011. Six studies were included in the meta-analysis, with a total of 359 keloid cases and 493 healthy controls. Meta-analysis results, respectively in the PCR-reverse dot blot and PCR-RFLP subgroups, showed significant associations between P53 Arg72Pro polymorphism and susceptibility to keloid in the comparisons of Pro allele vs Arg allele (odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.45-3.60; OR = 0.74, 95%CI = 0.56-0.98); Pro/Pro vs Pro/Arg + Arg/Arg (OR = 2.91, 95%CI = 1.88-4.53; OR = 0.54, 95%CI = 0.32-0.92); Pro/Pro vs Arg/Arg (OR = 2.79, 95%CI = 1.54-5.06; OR = 0.51, 95%CI = 0.28-0.92); Pro/Pro vs Pro/Arg (OR = 2.85, 95%CI = 1.75-4.63; OR = 0.57, 95%CI = 0.32-0.99). We conclude that the Pro allele of P53 Arg72Pro polymorphism is a risk factor for keloids in the Chinese population.

Environmental selection and epistasis in an empirical phenotype-environment-fitness landscape.

Fitness landscapes, mappings of genotype/phenotype to their effects on fitness, are invaluable concepts in evolutionary biochemistry. Although widely discussed, measurements of phenotype-fitness landscapes in proteins remain scarce. Here, we quantify all single mutational effects on fitness and phenotype (EC50) of VIM-2 ß-lactamase across a 64-fold range of ampicillin concentrations. We then construct a phenotype-fitness landscape that takes variations in environmental selection pressure into account. We found that a simple, empirical landscape accurately models the ~39,000 mutational data points, suggesting that the evolution of VIM-2 can be predicted on the basis of the selection environment. Our landscape provides new quantitative knowledge on the evolution of the ß-lactamases and proteins in general, particularly their evolutionary dynamics under subinhibitory antibiotic concentrations, as well as the mechanisms and environmental dependence of non-specific epistasis.

Antioxidants add protection to a broad-spectrum sunscreen.

BACKGROUND: Exposure of human skin to ultraviolet radiation (UVR) results in erythema, pigment darkening, skin cancer and photoageing. In addition to conventional organochemical and the physical-mineral type sunscreens (SS), other non-SS protective strategies have been investigated, including antioxidants (AOx) and topical DNA repair enzymes. AIM: To investigate whether AOx could improve the protection provided by a broad-spectrum sunscreen (SS) preparation. METHODS: Volunteers were exposed to repetitive solar-simulated (ss)UVR at 1.5 times minimal erythema dose for four consecutive days. Thirty minutes before each exposure and 6, 24 and 48 h after the last exposure, the test materials [vehicle, SS (sun protection factor 25) alone, AOx alone and SS plus AOx] were applied to four different sites. Another two sites received ssUVR only, or SS plus AOx only, and a third site was left untreated (neither ssUVR or product). Erythema and pigmentation were measured using a Mexameter. Biopsy specimens were taken 72 h after the last irradiation. The thickness of the stratum corneum and epidermis were measured by microscopy. Expression of cytokeratins (CKs), matrix metalloproteinases (MMPs) and CD1a-positive Langerhans cells (LCs) analysed by immunohistochemical staining, and relative expression levels were compared between all seven sites. RESULTS: AOx alone did not reduce erythema. There was a significant reduction in pigmentation, and the product almost completely protected against LC depletion. AOx plus SS gave better protection against pigment formation and CK5/6 induction than SS alone. AOx alone protected against ssUVR-induced hyperproliferation, as shown by epidermal thickness and CK16 biomarkers, and was better than SS alone. Interestingly, although protection against induction of MMP-9, a marker of photoageing, did not reach significance when either SS or AOx were applied separately, there was complete protection against MMP-9 induction when these were combined. CONCLUSIONS: Non-SS materials such as AOx can contribute significantly to sun protection when added to a broad-spectrum SS and applied topically to human skin in vivo.