Norsesquiterpenes from the Latex of Euphorbia dentata and Their Chemical Defense Mechanisms against Helicoverpa armigera.

Euphorbia dentata (Euphorbiaceae), an invasive weed, is rarely eaten by herbivorous insects and could secrete a large amount of white latex, causing a serious threat to local natural vegetation, agricultural production and human health. In order to prevent this plant from causing more negative effects on humans, it is necessary to understand and utilize the chemical relationships between the latex of E. dentata and herbivorous insects. In this study, three new norsesquiterpenes (1-3), together with seven known analogues (4-10), were isolated and identified from the latex of E. dentata. All norsesquiterpenes (1-10) showed antifeedant and growth-inhibitory effects on H. armigera with varying levels, especially compounds 1 and 2. In addition, the action mechanisms of active compounds (1-3) were revealed by detoxifying enzyme (AchE, CarE, GST and MFO) activities and corresponding molecular docking analyses. Our findings provide a new idea for the development and utilization of the latex of E. dentata, as well as a potential application of norsesquiterpenes in botanical insecticides.

Efficacy of acupuncture combined with active exercise training in improving pain and function of knee osteoarthritis individuals: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to investigate the clinical efficacy of acupuncture combined with active exercise training in improving pain and function of knee osteoarthritis (KOA) individuals. DATA SOURCES: PubMed, EMBASE, The Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang Data, Technology Periodical Database and China Biology Medicine were searched from their inceptions to April 5, 2023. REVIEW METHODS: We analyzed trials of acupuncture combined with active exercise training for KOA. The included studies were of high quality (Jadad ≥ 4) and RCTs. Study selection, data extraction, risk of bias and quality assessment were independently performed by two reviewers. We performed systematic analyses based on different outcome measures, including total efficiency rate, visual analogue scale (VAS), the Western Ontario and Mcmaster Universities Osteoarthritis Index (WOMAC), the Lysholm Knee Scale (LKS) and range of motion (ROM). We used Review Manager 5.3 and Stata/MP 14.0 to analyze the data. And it was verified by trial sequence analysis (TSA). If I2 > 50% and p < 0.05, we performed sensitivity analysis and subgroup analysis to find the source of heterogeneity. Publication bias was studied by funnel plot and Egger's test was used to verify it. RESULTS: Full 11 high-quality studies (Jadad ≥ 4) including 774 KOA individuals were included in this review for meta-analysis. The results showed that acupuncture combined with active exercise training (combined group) was superior to the acupuncture group in improving the total effective rate [RR = 1.13, 95%CI (1.05, 1.22), I2 = 0%, P = 0.70], reducing the pain level (VAS) [MD = - 0.74, 95%CI (- 1.04, - 0.43), I2 = 68%, P < 0.05], improving knee joint function (WOMAC) [MD = - 6.97, 95%CI (- 10.74, - 3.19), I2 = 76%, P < 0.05] and improving joint range of motion (ROM) [MD = 6.25, 95%CI (2.37, 10.04), I2 = 0%, P = 0.71]. Similarly, the combined group showed significant improvements in the total effective rate [RR = 1.31, 95% CI (1.18, 1.47), I2 = 48%, P = 0.10], pain (VAS) [MD = 1.42, 95% CI (- 1.85, - 1.00), I2 = 65%, P = 0.02] and knee function (WOMAC) [MD = 7.05, 95% CI (- 11.43, - 2.66), I2 = 86%, P < 0.05] compared with the non-acupuncture group. CONCLUSION: The combined effect of all studies showed significant benefits of acupuncture combined with active exercise training in improving the total effective rate, reducing pain, promoting recovery of knee function and expanding range of motion. However, some evaluation indicators are highly subjective and need to be further confirmed by more objective and evidence-based high-quality RCTs in future. SYSTEMATIC REVIEW REGISTRATION: [PROSPERO], identifier [No. CRD42023425823].

Phenylpropanoid amides from Solanum rostratum and their phytotoxic activities against Arabidopsis thaliana.

Introduction: Solanum rostratum, an annual malignant weed, has seriously damaged the ecological environment and biodiversity of invasion area. This alien plant gains a competitive advantage by producing some new phytotoxic substances to inhibit the growth of native plants, thus achieving successful invasion. However, the chemical structures, inhibitory functions and action mechanisms of phytotoxic substances of S. rostratum remain unclear. Methods: In this study, to clarify the chemical structures of phytotoxic substances from S. rostratum, we isolated phenylpropanoid amides from the plant. Their structures were identified by comprehensive HR-ESIMS, NMR and ECD data. And the inhibitory functions of isolated phenylpropanoid amides on one model plant (Arabidopsis thaliana) were also investigated. In addition, the action mechanisms of active phenylpropanoid amides were revealed by antioxidant-related enzymes [Catalase (CAT), Peroxidase (POD), Superoxide dismutase (SOD)] activities and corresponding molecular docking analyses. Results and Discussion: Phytochemical research on the whole plant of S. rostratum led to the isolation and identification of four new phenylpropanoid amides (1-4), together with two known analogues (5-6). All the compounds showed phytotoxic effects with varying levels on the seed germination and root elongation of one model plant (Arabidopsis thaliana), especially compound 2 and 4. Likewise, compounds 2 and 4 displayed potent inhibitory effects on antioxidant-related enzyme (POD). In addition, compounds 2 and 4 formed common conventional hydrogen bonds with residues Ala34 and Ser35 in POD revealed by molecular docking analyses. These findings not only helped to reveal the invasion mechanism of S. rostratum from the perspective of "novel weapons hypothesis", but also opened up new ways for the exploitation and utilization of S. rostratum.

Metabolic profiles in the xylem sap of Brassica juncea exposed to cadmium.

Metabolic profiles in xylem sap are considered a fundamental mechanism for Cadmium (Cd) detoxification in plants. However, the metabolic mechanism of Brassica juncea xylem sap in response to Cd is still unclear. Here, we investigated the effects on the metabolomics of B. juncea xylem sap treated with Cd at different times by utilizing a nontargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics method for further elucidating the response mechanism of Cd exposure. The findings indicated that 48 h and 7 days Cd exposure caused significant differences in metabolic profiles of the B. juncea xylem sap. Those differential metabolites are primarily involved in amino acids, organic acids, lipids, and carbohydrates, and most of them were downregulated, which played essential roles in response to Cd stress. Furthermore, B. juncea xylem sap resisted 48-h Cd exposure via regulation of glycerophospholipid metabolism, carbon metabolism, aminoacyl-tRNA biosynthesis, glyoxylate and dicarboxylate metabolism, linoleic acid metabolism, C5-branched dibasic acid metabolism, alpha-linolenic acid metabolism, cyanoamino acid metabolism, ABC transporters, biosynthesis of amino acids, and pyrimidine metabolism; whereas alpha-linolenic acid metabolism, glycerophospholipid metabolism, photosynthesis, and oxidative phosphorylation were regulated for resisting 7-day Cd exposure.

Exogenous proline mitigates toxic effects of cadmium via the decrease of cadmium accumulation and reestablishment of redox homeostasis in Brassica juncea.

BACKGROUND: As a vital osmoticum, proline has an important role in enhancing the tolerance of plants to environmental stress. It is unclear whether the application of exogenous proline can improve the tolerance of Brassica juncea to cadmium (Cd). RESULTS: This study investigated the effects of different concentrations of proline (20, 40, 60, 80, and 100 mg/L) under Cd stress at different times (0 d, 2 d, and 7 d) on the growth and physiology of B. juncea. Treatment with exogenous proline not only increased the content of proline in B. juncea but also alleviated Cd-induced seedling growth inhibition via the maintenance of higher photosynthetic pigment content and cell viability and a decrease in the content of Cd. Moreover, it increased the activities of antioxidant enzymes and the glutathione/glutathione disulfide ratio to reduce the accumulation of reactive oxygen species. Compared with other concentrations, 60 mg/L of exogenous proline was the most effective at mitigating Cd toxicity in B. juncea. CONCLUSIONS: Exogenous proline treatment enhanced the tolerance to Cd via a decrease in Cd accumulation and reestablishment of the redox homeostasis in B. juncea.

Prognostic value of circulating tumor cells and its association with the expression of cancer stem cells in nasopharyngeal carcinoma patients.

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process and the detection of CTCs has been widely used clinically. In addition, cancer stem cells (CSCs) are the source of distant metastasis. However, the relationship between CTCs and CSCs in nasopharyngeal carcinoma (NPC) patients was largely unknown. A total of 93 NPC patients were enrolled in this study. The CTCs in the peripheral blood were detected. The expression of ALDH1A1 in the tumor tissues of the corresponding patients was detected using immunohistochemistry (IHC). The prognostic value of CTCs level and the correlation with the expression of ALDH1A1 was evaluated. Data showed that the detection of CTCs was positively correlated with metastasis (p<0.001). The positive detection of CTCs was also associated with poor overall survival (p=0.025). CTCs ≥2 demonstrated good specificity and sensitivity in predicting distant metastasis, while CTCs ≥8 demonstrated better specificity and sensitivity in predicting prognosis than CTCs ≥2. Furthermore, we found that there was a positive relationship between the detection of CTCs and the expression of ALDH1A1 (p=0.001). The prognosis analysis also demonstrated that high ALDH1A1 expression was correlated with poor overall survival (p=0.006). Our study demonstrated a positive correlation between the CTCs and the expression of CSCs, both were positively correlated with metastasis and poor prognosis. These results indicated that the CTCs might indirectly reflect the expression of CSCs.

The role of Glutathione-S-transferases in phoxim and chlorfenapyr tolerance in a major mulberry pest, Glyphodes pyloalis walker (Lepidoptera: Pyralidae).

Glyphodes pyloalis Walker is a destructive pest on mulberry trees and poses a significant threat to the sericultural industry in China. Phoxim and chlorfenapyr are two commonly used insecticides in mulberry fields. Glutathione-S-transferases (GSTs) comprise a multifunctional protein superfamily that plays important roles in the detoxification of insecticides and xenobiotic compounds in insects. However, whether GSTs participate in the tolerance of phoxim and chlorfenapyr in G. pyloalis is still unknown. To better understand the mechanism of insecticide tolerance in G. pyloalis, the enzymatic activity of GSTs was evaluated under phoxim and chlorfenapyr exposure, respectively. GST enzyme activity was significantly increased after 12, 36 and 48 h of phoxim treatment and 12, 24, 36 and 48 h of chlorfenapyr treatment. Subsequently, eighteen GST genes were identified from the larvae transcriptome of G. pyloalis. Among these, ten GpGSTs had GSH-binding sites and fifteen GpGSTs had variable hydrophobic substrate-binding sites. The expression levels of Delta-GpGST and Epsilon-GpGST genes were significantly influenced by phoxim and chlorfenapyr treatment, and by the time post insecticide application. Furthermore, after silencing GpGST-E4, the mortality rate of G. pyloalis larvae was increased when they were exposed to chlorfenapyr, but it did not significantly alter when the larvae were exposed to phoxim. Our results indicated the vital roles of GpGSTs in the tolerance of insecticides and this action depends on the categories of insecticides. The present study provides a theoretical basis for elucidating insecticide susceptibility and promotes functional research on GST genes in G. pyloalis.

The elemental defense effect of cadmium on Alternaria brassicicola in Brassica juncea.

BACKGROUND: The elemental defense hypothesis states a new defensive strategy that hyperaccumulators defense against herbivores or pathogens attacks by accumulating heavy metals. Brassica juncea has an excellent ability of cadmium (Cd) accumulation. However, the elemental defense effect and its regulation mechanism in B. juncea remain unclear. RESULTS: In this study, we profiled the elemental defense effect and the molecular regulatory mechanism in Cd-accumulated B. juncea after Alternaria brassicicola infection. B. juncea treated with 180 mg Kg- 1 DW CdCl2 2.5H2O exhibited obvious elemental defense effect after 72 h of infection with A. brassicicola. The expression of some defense-related genes including BjNPR1, BjPR12, BjPR2, and stress-related miRNAs (miR156, miR397, miR398a, miR398b/c, miR408, miR395a, miR395b, miR396a, and miR396b) were remarkably elevated during elemental defense in B. juncea. CONCLUSIONS: The results indicate that Cd-accumulated B. juncea may defend against pathogens by coordinating salicylic acid (SA) and jasmonic acid (JA) mediated systemic acquired resistance (SAR) and elemental defense in a synergistic joint effect. Furthermore, the expression of miRNAs related to heavy metal stress response and disease resistance may regulate the balance between pathogen defense and heavy metal stress-responsive in B. juncea. The findings provide experimental evidence for the elemental defense hypothesis in plants from the perspectives of phytohormones, defense-related genes, and miRNAs.

Sublethal effects of organophosphorus insecticide phoxim on patch time allocation and oviposition behavior in a parasitoid wasp Meteorus pulchricornis.

Parasitoid wasps are key agents for controlling insect pests in integrated pest management programs. Although many studies have revealed that the behavior of parasitic wasps can be influenced by insecticides, the strategies of patch time allocation and oviposition have received less attention. In the present study, we forced the endoparasitoid Meteorus pulchricornis to phoxim exposure at the LC30 and tested the foraging behavior within patches with different densities of the host, the larvae of the tobacco cutworm Spodoptera litura. The results showed that phoxim treatment can significantly increase the patch-leaving tendency of female wasps, while host density had no impact. The number of oviposition and the number of previous patch visits also significantly influenced the patch time allocation decisions. The occurrence of oviposition behavior was negatively affected by phoxim exposure; however, progeny production was similar among patches with different host densities. Phoxim exposure shaped the offspring fitness correlates, including longer durations from cocoon to adult wasps, smaller body size, and shorter longevity. The findings of the present study highlight the sublethal effects that reduce the patch residence time and the fitness of parasitoid offspring, suggesting that the application of phoxim in association with M. pulchricornis should be carefully schemed in agroecosystems.

Zuogui Pill Ameliorates Glucocorticoid-Induced Osteoporosis through ZNF702P-Based ceRNA Network: Bioinformatics Analysis and Experimental Validation.

Glucocorticoid-induced osteoporosis (GIOP) is a musculoskeletal disease with increased fracture risk caused by long-term application of glucocorticoid, but there exist few effective interventions. Zuogui Pill (ZGP) has achieved clinical improvement for GIOP as an ancient classical formula, but its molecular mechanisms remain unclear due to scanty relevant studies. This study aimed to excavate the effective compounds and underlying mechanism of ZGP in treating GIOP and construct relative ceRNA network by using integrated analysis of bioinformatics analysis and experimental validation. Results show that ZNF702P is significantly upregulated in GIOP than normal cases based on gene chip sequencing analysis. Totally, 102 ingredients and 535 targets of ZGP as well as 480 GIOP-related targets were selected, including 122 common targets and 8 intersection targets with the predicted mRNAs. The ceRNA network contains one lncRNA (ZNF702P), 6 miRNAs, and 8 mRNAs. Four hub targets including JUN, CCND1, MAPK1, and MAPK14 were identified in the PPI network. Six ceRNA interaction axes including ZNF702P-hsa-miR-429-JUN, ZNF702P-hsa-miR-17-5p/hsa-miR-20b-5p-CCND1, ZNF702P-hsa-miR-17-5p/hsa-miR-20b-5p-MAPK1, and ZNF702P-hsa-miR-24-3p-MAPK14 were obtained. By means of molecular docking, we found that all the hub targets could be effectively combined with related ingredients. GO enrichment analysis showed 649 biological processes, involving response to estrogen, response to steroid hormone, inflammatory response, macrophage activation, and osteoclast differentiation, and KEGG analysis revealed 102 entries with 36 relative signaling pathways, which mainly contained IL-17 signaling pathway, T cell receptor signaling pathway, FoxO signaling pathway, the PD-L1 expression and PD-1 checkpoint pathway, MAPK signaling pathway, TNF signaling pathway, Estrogen signaling pathway, and Wnt signaling pathway. Our experiments confirmed that ZNF702P exhibited gradually increasing expression levels during osteoclast differentiation of human peripheral blood monocytes (HPBMs) induced by RANKL, while ZGP could inhibit osteoclast differentiation of HPBMs induced by RANKL in a concentration-dependent manner. Therefore, by regulating inflammatory response, osteoclast differentiation, and hormone metabolism, ZGP may treat GIOP by regulating hub target genes, such as JUN, CCND1, MAPK1, and MAPK14, and acting on numerous key pathways, which involve the ZNF702P-based ceRNA network.

Metabolic Profiles of Brassica juncea Roots in Response to Cadmium Stress.

Brassica juncea has great application potential in phytoremediation of cadmium (Cd)-contaminated soil because of its excellent Cd accumulating and high biomass. In this study, we compared the effects of Cd under 48 h and 7 d stress in roots of Brassica juncea using metabolite profiling. The results showed that many metabolic pathways and metabolites in Brassica juncea roots were altered significantly in response to Cd stress. We found that significant differences in levels of amino acids, organic acids, carbohydrates, lipids, flavonoids, alkaloids, and indoles were induced by Cd stress at different times, which played a pivotal role in the adaptation of Brassica juncea roots to Cd stress. Meanwhile, Brassica juncea roots could resist 48 h Cd stress by regulating the biosynthesis of amino acids, linoleic acid metabolism, aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, ABC transporters, arginine biosynthesis, valine, leucine and isoleucine biosynthesis, and alpha-linolenic acid metabolism; however, they regulated alpha-linolenic acid metabolism, glycerophospholipid metabolism, ABC transporters, and linoleic acid metabolism to resist 7 d Cd stress. A metabolomic expedition to the response of Brassica juncea to Cd stress will help to comprehend its tolerance and accumulation mechanisms of Cd.

Benwamycins A-G, Trialkyl-Substituted Benzene Derivatives from a Soil-Derived Streptomyces.

Seven new trialkyl-substituted benzene derivatives named benwamycins A-G (1-7), together with three known congeners, 8-10, were isolated from culture broth of the soil-derived Streptomyces sp. KIB-H1471. Their structures were elucidated by using 1D and 2D NMR analyses in combination with HRESIMS data. The absolute configurations of 1-9 were determined by chemical conversion and comparison of circular dichroism spectra and confirmed for 1 by single-crystal X-ray crystallography. Compounds 6 and 7 have a unique γ-pyrone-like ring on one side chain. Compounds 2 and 6 inhibited human T cell proliferation with IC50 values of 14.3 and 12.5 µM, respectively, without obvious cytotoxicity for naïve human T cells. Compounds 3 and 6 could weakly enhance insulin-stimulated glucose uptake.

Secondary Metabolites from Solanum rostratum and Their Antifeedant Defense Mechanisms against Helicoverpa armigera.

Solanum rostratum is a worldwide malignant invasive weed, causing serious harm to the ecological environment and biodiversity. Strong chemical defense against herbivorous insects is supposed to be one of the successful invasive mechanisms of this exotic plant. However, the real defense components and their action mechanisms and distributions are still unknown. To address these problems, we bioassay-guided isolated compounds from the aerial part of S. rostratum and determined their structures using high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance, and electronic circular dichroism calculation. One new and seven known compounds were identified, and all of the isolates exhibited different levels of antifeedant activities, especially compounds 1 and 4. Consistently, compounds 1 and 4 displayed potent inhibitory effects on antifeedant-related enzymes (AchE and CarE). The action mechanisms of active compounds 1 and 4 were revealed by molecular docking and molecular dynamic simulation studies. Furthermore, the distributions of the active compounds in leaves, stems, and flowers were also analyzed by liquid chromatography-mass spectrometry.

Long-term Fiber Photometry for Neuroscience Studies.

Fiber photometry is a sensitive and easy way to detect changes in fluorescent signals. The combination of fiber photometry with various fluorescent biomarkers has substantially advanced neuroscience research over the last decade. Despite the wide use of fiber photometry in biomedical fields, the lack of a detailed and comprehensive protocol has limited progress and sometimes complicated the interpretation of data. Here, we describe detailed procedures of fiber photometry for the long-term monitoring of neuronal activity in freely-behaving animals, including surgery, apparatus setup, data collection, and analysis.

An updated comparison of high- and low-viscosity cement vertebroplasty in the treatment of osteoporotic thoracolumbar vertebral compression fractures: A retrospective cohort study.

OBJECTIVE: This study mainly aimed to evaluate complications of cement leakage for osteoporotic thoracolumbar vertebral compression fractures by PVP using HVC, and access the clinical efficacy. METHODS: Between May 2013 and June 2015, 66 patients with osteoporotic thoracolumbar vertebral compression fractures, who underwent PVP (36 HVC and 30 LVC) in our hospital, were enrolled. Cement leakage, Visual Analog Scale (VAS), Oswestry Disability Index (ODI), refracture of the cemented vertebrae, and adjacent vertebral fractures were evaluated. The follow-up time was 1 year. RESULTS: The overall cement leakage rate was 30.55% in the HVC group, lower than 77.77% obtained in the LVC group (P = 0.00). The incidence rates of cement leakage into paravertebral area (P = 0.02) and vein (P = 0.04) in the HVC group were significantly lower than those of the LVC group; however, no differences were found for disc space (P = 0.72) and intraspinal space (P = 0.58). There were no differences in VAS, ODI, refracture of cemented vertebrae, and adjacent vertebral fracture between the two groups (P > 0.05). CONCLUSIONS: PVP using HVC not only can reduce cement leakage, especially in the paravertebral area and peripheral vein, but also has satisfactory clinical effect.

[Clinical effect of staged repair and reconstruction of multiple ligament injuries in knee joints].

OBJECTIVE: To evaluate clinical outcomes of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) reconstruction under arthroscopy combined with limited open repair of medial collateral ligament (MCL) for the treatment of multiple ligament injuries of knee joints. METHODS: From March 2006 and June 2012,the data of 14 patients (14 knees) with multiple injuries of ACL, PCL, and MCL were collected. There were 8 males and 6 females with an average age of (31.8 +/- 8.1) years old (ranged, 20 to 49 years old). All the patients were performed with X-ray and MRI examination, and the results showed that 10 patients had combined with injuries of anterior cruciate ligament (ACL), posterior cruciate ligament (PCL) and medial collateral ligament (MCL); 4 patients had ALC,PCL and posterolateral corner (PLC) injuries. Four patients had medial meniscus injuries and 2 patients had lateral meniscus injuries. The MCL,PLC and meniscus injuries were treated with operation on the first stage, and functional exercises were performed 3 weeks after fixation. The reconstruction operation of ACL and (or) PCL was performed at the second stage under arthroscopy 3 to 6 months later when the movement range of knee joint recovered to the normal level with obvious relaxation. RESULTS: All incisions healed by primary intention. All the patients were followed up with a mean duration of 48.9 months (ranged, 24 to 80 months). The Lysholm score was improved from preoperative 19.6 +/- 0.9 to the latest follow-up 87.1 +/- 2.8 (t=12.3, P<0.01). The International Knee Documentation Committee (IKDC) rating: 9 cases nearly recovered to normal, 5 cases were abnormal. CONCLUSION: For multiple ligament injuries in the knee, staged repair and reconstruction can effectively restore knee joint stability and function.

Prevalence and genotype distribution of human papillomavirus among Hakka women in China.

BACKGROUND: Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. HPV genotypes are associated with varying degrees of pathogenicity. To better formulate strategies for cervical cancer prevention, we investigated the population-specific distribution of HPV genotypes, including those with high carcinogenicity. METHODS: From January to December 2012, a cervical cancer-screening program for HPV infection in Hakka women of Heyuan City Guangdong province was conducted. Of 736,000 women residents, 8,284 volunteers were recruited. The cytology specimens of 107 women were not adequate and excluded. Thus, 8,177 women submitted to polymerase chain reaction (PCR) sequencing of 16 HPV genotypes via MassARRAY spectrometry. RESULTS: Risk stratification based on genotypes indicated that the prevalence of overall, high-risk, and low-risk HPV infections was 12.27%, 14.20%, and 0.79%, respectively. Of the 1,003 women positively infected, 82.75% were infected with a single HPV type; 17.25% were infected with ≥2 types. Analysis revealed a U-shaped curve in HPV prevalence that correlated with age group, with peaks at ages 18-24 y (22.03%) and 60-65 y (25%). The most frequently detected HPV genotype was HPV-52 (26.81%), and then HPV-16 (17.54%), HPV-58 (14.25%), HPV-18 (10.16%), HPV-68 (8.27%), HPV-39 (5.68%), and HPV-51 (5.38%). CONCLUSIONS: HPV-52 is the most prevalent genotype infecting Hakka women. Therefore, vaccination against HPV-52 is imperative. The prevalence of HPV infection is highest in the younger (18-24 y) and older (60-65 y) age groups, indicating that screening for HPV in Hakka women should be performed early and maintained in the elderly.

Nonlinear dose-response relationship between radon exposure and the risk of lung cancer: evidence from a meta-analysis of published observational studies.

Although radon exposure (RE) has been confirmed to increase the risk of lung cancer (LC), questions remain about the shape of the dose-response relationship between RE and the risk of LC. We carried out a dose-response meta-analysis to investigate and quantify the potential dose-response association between residential and occupational exposure to radon and the risk of LC. All cohort and case-control studies published in English and Chinese on Embase, PubMed, and China National Knowledge Infrastructure (CNKI) digital databases through November 2013 were identified systematically. We extracted effect measures (relative risk, odds ratio, standardized mortality ratio, standardized incidence ratio, or standardized rate ratio) from individual studies to generate pooled results using meta-analysis approaches. We derived meta-analytic estimates using random-effects models taking into account the correlation between estimates. Restricted cubic splines and generalized least-squares regression methods were used to model a potential curvilinear relationship and to carry out a dose-response meta-analysis. Stratified analysis, sensitivity analysis, and assessment of bias were performed in our meta-analysis. Sixty publications fulfilling the inclusion criteria for this meta-analysis were finally included. Occupational RE was associated with LC [risk ratio 1.86, 95% confidence interval (CI)=1.67-2.09; I²=92.2%; 27 prospective studies], for pooled risk estimate of the: standardized mortality ratio [2.00 (95% CI=1.82-2.32)]; standardized incidence ratio [1.45 (95% CI=1.20-1.74)]; relative risk [2.10 (95% CI=1.64-2.69)]. In a subgroup analysis of uranium miners and residents exposed to occupational uranium, the summary risk was 2.23 (95% CI=1.86-2.68) and 1.23 (95% CI=1.05-1.44). The overall meta-analysis showed evidence of a nonlinear association between RE and the risk of LC (P(nonlinearity)<0.014); in addition, the point value of residential radon also improved the results quantitatively, where odds ratios were 1.11 (95% CI=1.07-1.15) and 1.21 (95% CI=1.14-1.29) when the radon concentration was at the point of 100 and 200 Bq/m³ compared with the lowest. For 17 prospective studies with at least three categories of occupational cumulative radon dose, the dose-risk model estimated a risk ratio of 1.26 (95% CI=1.21-1.30) for 100 working level months and 1.51 (95% CI=1.38-1.65) for 200 working level months, respectively. The assessment of risk of bias within individual studies and across studies indicated risk that was unlikely to alter these results markedly. This meta-analysis shows a nonlinear dose-response association between environmental RE and the risk of LC. This increased risk is particularly apparent when the cumulative exposure to radon is well beyond that resulting from exposure to the recommended limit concentration for a prolonged period of time.

The clinical value of serum hepatocyte growth factor levels in patients undergoing primary radiotherapy for glioma: effect on progression-free survival.

Hepatocyte growth factor (HGF) has been shown to be overexpressed in gliomas, and high-grade gliomas (glioblastoma multiforme) express more HGF than lower-grade astrocytoma, and HGF enhances their resistance to radiotherapy. To examine the effect of serum HGF levels on the likelihood of response to radiotherapy and the disease-free survival in patients with glioma, the blood samples of the patients were collected before commencing treatment and serum HGF was measured by quantitative ELISA in 48 patients with glioma grade I-IV, and all patients underwent primary conventionally fractionated radiotherapy. For statistical analysis, SPSS Version 13.0 software was used. Thirty-eight of the 48 patients had a response to treatment, and ten patients had persistent disease at 3 months. Overall, the median serum HGF level was 1,219.5 pg/ml (range 650.4-2,264.7 pg/ml). Eight patients with local failure had HGF levels >1,219.5 pg/ml, and 28 patients with response had serum HGF level of ≤ 1,219.5 pg/ml (P = 0.01). The median time to progression was 6 months in patients with HGF level of >1,219.5 pg/ml compared with 17 months in patients with HGF level of ≤ 1,219.5 pg/ml (log-rank, P = 0.041). In multivariate analysis, serum HGF, the KPS, tumour size and pathological grade, but not the patient's age, gender and oligodendroglial component influenced the progression-free survival. Elevated pre-therapeutic serum HGF levels are associated with poor response and a shorter time to progression in patients with glioma undergoing primary radiotherapy.

Three new lignan glycosides from the fruits of Forsythia suspense.

Two new lignan glycosides forsythiayanoside A (1) and forsythiayanoside B (2), one new stereoisomer of lignan glycoside (+)-8-hydroxyepipinoresinol-4-O-ß-D-glucopyranoside (3), together with seven known compounds (4-10), were isolated from the fruits of Forsythia suspense (Thunb.) Vahl. Compounds 4 and 10 were isolated from this species for the first time. The structures of 1-3 were elucidated on the basis of chemical and spectral analyses, including 1D and 2D NMR data and HR-ESI-MS. The absolute configurations were determined by the circular dichroism method. All isolates were tested for their cytotoxicities against five human cancer cell lines (A549, Colo-205, Hep-3B, HL60, and KB). In particular, compound 3 showed significant cytotoxicity with IC50 values of 9.48, 7.75, 0.59, 4.06, and 38.38 µM, respectively.