The Polysaccharides from Pinellia ternata and Their Derivatives: Preparation, Structure Characteristics, and Activities in Vitro.

Three polysaccharides, PTC, PTH, and PTB, were extracted from Pinellia ternata using three different extraction conditions: room temperature water, hot water, and 2 % Na2CO3 solution. PTC and PTH were composed of rhamnose, glucose, galactose, mannose, glucuronic acid, galacturonic acid, and arabinose, which combine to form complex structures. PTB was composed solely of glucose and rhamnose. Further analysis indicated that PTC and PTB exhibited triple-helix structures. PTC showed the highest scavenging capacity against DPPH, superoxide anion, and hydroxyl radicals, with half maximal inhibitory concentrations (IC50) of 1004.1, 1584.1, and 1584.1 µg/mL, respectively. Additionally, PTC, PTH, and PTB were subjected to sulfation, phosphorylation, and selenization, resulting in the production of nine derivates. The distinctive absorptive bands of these derivates were determined through infrared spectroscopy. Selenized and sulfated derivates have shown significant antitumor and immunoenhancing properties. Our findings revealed that at 400 µg/mL, the inhibition rate of selenated PTB on HeLa cells was 54.2 % and that on HepG2 cells was 43.1 %. Additionally, selenized PTC displayed significant immunoenhancing activity, with a proliferation rate of 63.7 % at 400 µg/mL in RAW264.7 cells. These results provide valuable evidence supporting the consideration of polysaccharides from Pinellia ternata as a potential candidate for the development of antineoplastic drugs.

Electrophysiological and behavioral responses of Tamarixia radiata (Hymenoptera: Eulophidae) to volatiles of nymphal Diaphorina citri (Hemiptera: Liviidae).

Huanglongbing (HLB), a devastating citrus disease caused by Candidatus Liberibacter asiaticus, is efficiently vectored by the Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Liviidae). Tamarixia radiata (Waterston) plays a crucial role as an ectoparasitoid, preying on D. citri nymphs. By collecting and identifying headspace volatiles from fifth instar nymphs of D. citri using a gas chromatograph-mass spectrometer (GC-MS), we obtained a collection of 9 volatile compounds. These compounds were subsequently chosen to investigate the electrophysiological and behavioral responses of female T. radiata. At a concentration of 10 µg/µl, 9 compounds were compared with cis-3-hexen-1-ol (control), resulting in trans-2-nonenal inducing the highest relative electroantennogram (EAG) value, followed by hexanal, heptanal, n-heptadecane, tetradecanal, n-tetradecane, n-pentadecane, 1-tetradecanol, and 1-dodecanol. The top 5 EAG responses of female T. radiata to these compounds were further investigated through EAG dose-response experiments. The results showed positive dose-responses as concentrations increased from 0.01 to 10 µg/µl. In Y-tube olfactometer bioassays, female T. radiata exhibited a preference for specific compounds. They were significantly attracted to tetradecanal at a concentration of 10 µg/µl and trans-2-nonenal at 0.01 µg/µl, while no significant attraction was observed toward hexanal, heptanal, or n-heptadecane. Our report is the first to demonstrate that volatiles produced by D. citri nymphs attract T. radiata, which suggests that this parasitoid may utilize nymph volatiles to locate its host.

Pharmacokinetics, mass balance, and metabolism of [14C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension.

TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED), which currently is undergoing phase II clinical trials in China. In this single-center, single-dose, nonrandomized, and open design study, radiolabeled [14C]TPN171 was used to investigate the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of TPN171 in 6 healthy Chinese male volunteers. Each volunteer was administered a single oral suspension of 10 mg (100 µCi) of [14C]TPN171. We found that TPN171 was absorbed rapidly in humans with a peak time (Tmax) of 0.667 h and a half-life (t1/2) of approximately 9.89 h in plasma. Excretion of radiopharmaceutical-related components was collected 216 h after administration, accounting for 95.21% of the dose (46.61% in urine and 48.60% in feces). TPN171 underwent extensive metabolism in humans. Twenty-two metabolites were detected in human plasma, urine, and feces using a radioactive detector combined with a high-resolution mass spectrometer. According to radiochromatograms, a glucuronide metabolite of O-dealkylated TPN171 exceeded 10% of the total drug-related components in human plasma. However, according to the Food and Drug Administration (FDA) guidelines, no further tests are needed to evaluate the safety of this metabolite because it is a phase II metabolite, but the compound is still worthy of attention. The main metabolic biotransformation of TPN171 was mono-oxidation (hydroxylation and N-oxidation), dehydrogenation, N-dealkylation, O-dealkylation, amide hydrolysis, glucuronidation, and acetylation. Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites, and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent. According to the incubation data, M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9), followed by UGT1A7 and UGT1A10.

Outcomes of icotinib combined with concurrent chemoradiotherapy in locally advanced cervical cancer.

Concurrent chemoradiotherapy (CRT) based on cisplatin is recognized as the current standard treatment for locally advanced cervical cancer. The treatment of cervical cancer has reached a plateau in the last 20 years. Previous studies have proven that the epidermal growth factor receptor is correlated with chemo- and radioresistance and treatment failure. Hence, the purpose of this study was to investigate the efficacy and safety of icotinib combined with CRT in the treatment of locally advanced cervical cancer. Eligibility criteria included patients treated in the radiotherapy department of Taizhou Central Hospital of Zhejiang Province for stage IIB to IIIB cervical cancers who had not received anti-tumor treatment before and a performance status of 0 to 2. Patients were given icotinib 125 mg three times a day for 6 weeks, which was one week before the start of radiotherapy (500 centigrays in 28 fractions) and chemotherapy (40 mg/m2 administered weekly for 3-5 cycles). There were 29 patients who completed the I+CRT treatment, and it was tolerated well. The median follow-up time was 50 months and 27 patients (93.10%) achieved complete responses. The 5-year cumulative overall survival rate and disease-free survival rate were 58.4% and 60.9%, respectively. The treatment with I+CRT is safe and effective for locally advanced cervical cancer. As far as we know, this is the first study to report the 5-year survival rate of locally advanced cervical cancer with targeted therapy combined with chemoradiotherapy.

What is the impact of knee morphology on posterior cruciate ligament avulsion fracture in men and women: a case control study.

BACKGROUND: Several studies on the relationship between morphological parameters and traumatic diseases of the knee have already been conducted. However, few studies focused on the association between knee morphology and posterior cruciate ligament (PCL) avulsion fracture in adults. The objective of this study was to evaluate the impact of knee morphology on PCL avulsion fracture. METHODS: 76 patients (comprised 40 men and 36 women) with PCL avulsion fracture and 76 age- and sex-matched controls without PCL avulsion fracture were studied from 2012 to 2020. MRI measurements of the knee were acquired in the sagittal, coronal, and axial planes. The assessed measurements including intercondylar notch width index, coronal tibial slope, and medial/lateral posterior tibial slopes were compared between men and women, and between case and control groups respectively using independent sample t-tests. In addition, binary logistic regression analyses were used to identify independent risk factors of PCL avulsion fracture. RESULTS: Except notch width index (coronal) (p = 0.003) in the case groups, there was no statistical difference in the assessed measurements including notch width index (axial), coronal tibial slope, medial posterior tibial slope, and lateral posterior tibial slope between men and women in the case and control groups (p > 0.05). When female patients were analyzed, the notch width index (coronal) was significantly smaller (p = 0.0004), the medial posterior tibial slope (p = 0.018) and the lateral posterior tibial slope (p = 0.033) were significantly higher in the case group. The binary logistic regression analysis showed that the notch width index (coronal) (B = -0.347, OR = 0.707, p = 0.003) was found to be an independent factor of PCL avulsion fracture. However, none of the assessed measurements was found to have a statistical difference between the case and control groups in men (p > 0.05). CONCLUSIONS: Notch width index (coronal), medial posterior tibial slope, and lateral posterior tibial slope were found to affect PCL avulsion fracture in women, but no such measurements affected the PCL avulsion fracture in men. Furthermore, a smaller notch width index (coronal) in women was found to be a risk factor in PCL avulsion fracture.

Male papillomavirus infection and genotyping in the Qingyuan area.

BACKGROUND: This study aims to screen the male human papillomavirus (HPV) infection status and genotyping in Qingcheng District, Qingyuan City, Guangdong Province, China to provide a reference basis for formulating prevention strategies for HPV infection. METHODS: The present study collected urethral epithelium or scraped penile epidermis from high-risk male patients in Qingyuan People's Hospital during the last five years, extracted DNA fragments using the boiling method, and detected 23 types of HPV genotypes by PCR-reverse blot hybridization. RESULTS: The positive detection rate was 54.31% of 1044 males with high risk of HPV (567/1044). Among these males, the positive detection rate of HPV was the highest in patients initially diagnosed with warts, and the rate was 66.47%. Five main HPV types are identified as follows: HPV6 18.87% (197/1044), HPV11 10.25% (107/1044), HPV52 8.81% (92/1044), HPV16 6.90% (72/1044), and HPV51 5.08% (53/1044). Among these HPV-infected patients, single infection mainly by low-risk HPV6 and HPV11 accounted for 56.61% (321/567); high- and low-risk combined HPV co-infections accounted for 29.10% (165/567). The HPV infected patients was mainly between 21 and 40 years old, and the HPV infection rate was higher with increased age. CONCLUSIONS: The HPV infection rate in the Qingyuan area is higher than in other areas and the main infection is single infection. Furthermore, HPV52, HPV16, and HPV51 are the main high-risk infection types, while HPV6 and HPV11 are the main low-risk infection types.

Synergistic effect of glucocorticoids and IGF-1 on myogenic differentiation through the Akt/GSK-3ß pathway in C2C12 myoblasts.

Purpose: Glucocorticoids are the only therapeutics that can delay the progression of Duchenne musculardystrophy (DMD), the most prevalent type of inherited neuromuscular disorder in males. However, beyond theiranti-inflammatory effects, glucocorticoids have other underlying mechanisms that remain unclear. Moreover, muscleand circulating levels of insulin growth factor-1 (IGF-1) often decrease in response to glucocorticoids. Therefore, wehypothesized that glucocorticoids, either alone or in combination with IGF-1, can improve myogenic differentiation.Materials and methods: Established C2C12 myoblasts were employed as an in vitro model of myogenic differentiation,and myogenic differentiation markers, as assessed by Western blot (myogenin, MyoD, and MyHC protein expression),cellular morphology analysis (fusion index) and RT-PCR (MCK mRNA expression), were measured.Results: Myogenic differentiation markers were increased by glucocorticoid treatment. Furthermore, this effect was furtherenhanced by IGF-1, and these results suggest that glucocorticoids, either alone or together with IGF-1, can promotemyogenic differentiation. Akt and GSK-3ß play important roles in myogenic differentiation. Interestingly, the levels ofboth phosphorylated Ser473-Akt and phosphorylated Ser9-GSK-3ß were increased by glucocorticoid and IGF-1 cotreatment.Pharmacological manipulation with LY294002 and LiCl was employed to inhibit Akt and GSK-3ß, respectively.We found that cellular differentiability was inhibited by LY294002 and enhanced by LiCl, indicating that theAkt/GSK-3ß signaling pathway is activated by glucocorticoid and IGF-1 treatment to promote myogenic differentiation.Conclusions: Glucocorticoids together with IGF-1 promote myogenic differentiation through the Akt/GSK-3ßpathway. Thus, these results further our knowledge of myogenic differentiation and may offer a potential alternativestrategy for DMD treatment based on glucocorticoid and IGF-1.

Methyleugenol Potentiates Central Amygdala GABAergic Inhibition and Reduces Anxiety.

The central amygdala (CeA) plays a critical role in the expression of emotional behaviors, including pathologic anxiety disorders. The present study demonstrated that GABAergic inhibition in CeA was significantly increased by methyleugenol (ME), a natural constituent isolated from the essential oils of several plants. The electrophysiologic recordings showed that ME increased both tonic and miniature inhibitory postsynaptic GABAergic currents in CeA slices, especially the tonic currents, while the miniature excitatory postsynaptic currents were not affected. In the fear-induced anxiety animal model, both intraperitoneal injection or CeA-specific infusion of ME reduced the anxiety-like behaviors in mice, likely by facilitating the activation of A-type GABA receptors (GABAARs). These results reveal that GABAAR in the CeA can be a potential therapeutic target for the treatment of anxiety and that ME is capable of enhancing the GABAergic inhibition in CeA neurons for the inhibition of neuronal excitability.

Peri-conceptional or pregnancy exposure of HPV vaccination and the risk of spontaneous abortion: a systematic review and meta-analysis.

BACKGROUND: To assess whether the peri-conceptional or pregnancy exposure of human papillomavirus (HPV) vaccination would increase the risk of spontaneous abortion. METHODS: We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for clinical trials and observational studies that investigated the association between exposure of HPV vaccines (2vHPV, 4vHPV or 9vHPV) during peri-conceptional period or pregnancy and spontaneous abortion before 28 gestational weeks. We pooled data from 2vHPV, 4vHPV and 9vHPV separately. Subgroup analyses were conducted according to data sources, and raw data or adjusted data. RESULTS: Seven observational studies were eligible and all studies were low risk of bias. Meta-analyses suggested that 2vHPV vaccination did not increase the risk of spontaneous abortion regardless of exposure period during 90 days before last menstrual period (LMP) or pregnancy: risk ratio, 95% confidence intervals (RR, 95% CI), 1.15 (0.95-1.39), and 45 days before LMP or pregnancy: 1.28 (0.96-1.70). However, 2vHPV vaccination during Pre-45 days to LMP seemed to increase the risk of spontaneous abortion: 1.59 (1.04-2.45). The current evidence did not support the association between 4vHPV vaccination and spontaneous abortion regardless of exposure period during 45 days before LMP or pregnancy: 0.88 (0.73-1.06); and 45 days before LMP: 1.00 (0.80-1.24). Additionally, 9vHPV during within 30 days of conception also seemed to increase the risk: 2.04 (1.28-3.24). CONCLUSIONS: The association between peri-conceptional or pregnancy exposure of HPV vaccine and spontaneous abortion is still uncertain, and additional research is warranted to assess the impact of exposure of HPV vaccination on spontaneous abortion.

Digital gene expression profiling in larvae of Tribolium castaneum at different periods post UV-B exposure.

UV-B radiation is an important environmental factor. Exposure to excess UV-B radiation can cause serious effects on the development, survival, and reproduction of different organisms. Plants and animals have developed many different strategies to cope with UV-B-induced damage, but the physiological response of insects to UV-B remains unclear. In the present study, the red flour beetle Tribolium castaneum (Herbst) was used to assess the stress response of UV-B. The underlying molecular mechanisms were explored using RNA sequencing. We investigated the transcriptomic profile of T. castaneum larvae at 4 and 24 h after treatment with UV-B radiation via digital gene expression analysis. The 310 and 996 differentially expressed genes were detected at 4 and 24 h, respectively. Then the biological functions and associated metabolic processes of these genes were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The reliability of the data was verified using qRT-PCR. The results indicated that several differentially expressed genes are involved in antioxidation, DNA repair, protein folding, carbon flux diversion, and the extracellular matrix to protect against UV-B-induced damage. This study will increase our understanding of the molecular mechanism underlying insect response to UV-B radiation.

Molecular phylogenetics and historical biogeography of the tribe Lilieae (Liliaceae): bi-directional dispersal between biodiversity hotspots in Eurasia.

Background and Aims: The role played by the Qinghai-Tibet Plateau (QTP) in the organismal diversification and biogeography of plants in the Northern Hemisphere has attracted much attention from evolutionary biologists. Here we use tribe Lilieae (Liliaceae), including primarily temperate and alpine lineages with disjunct distributions in the North Temperate Zone, as a case study to shed light upon these processes. Methods: Using 191 taxa (five outgroup taxa) comprising more than 60 % of extant Lilieae species across the entire geographical range, we analyse phylogenetic relationships based on three plastid markers (matK, rbcL, rpl16) and nuclear ITS. Divergence time estimation and ancestral range reconstruction were further inferred. Key Results: The results support a monophyletic Lilieae divided into four clades. Lilium is nested within Fritillaria, which is paraphyletic and partitioned into two clades, New World and Old World, in the chloroplast DNA (cpDNA) analysis. Incongruences between the ITS and cpDNA trees may be explained by divergent ITS paralogues and hybridization. Lilieae originated around 40-49 (28-67) Mya and probably diversified in the QTP region with four major clades that were established during the Oligocene and the Early Miocene. Uplift of the QTP and climatic changes probably drove early diversification of Lilieae in the QTP region. A rapid radiation occurred during the Late Miocene and the Pleistocene, coinciding temporally with recent orogenic process in the QTP region and climatic oscillations. Several lineages dispersed out of the QTP. Conclusions: Lineage persistence and explosive radiation were important processes for establishing high species diversity of Lilieae in the QTP region. Both long-distance dispersal and migration across Beringia probably contributed to the modern distribution range of Lilieae. Our study shows that biotic interchanges between the QTP region and Irano-Turanian region and the Mediterranean Basin were bi-directional, suggesting the latter was a secondary centre of diversity.

Outcome and prognostic factors in cervical cancer patients treated with surgery and concurrent chemoradiotherapy: a retrospective study.

BACKGROUND: The objective of this study is to analyze the treatment outcome and secondary reactions in 98 patients with stage I-III cervical carcinoma who underwent postoperative radiotherapy. METHODS: From 2006 to 2014, 98 patients with stage I-III cervical carcinoma were treated with postoperative radiotherapy. The major histological type, found in 92.86% of the patients (91 cases), was squamous cell carcinoma. Patients were staged according to the 2002 TNM guidelines. The postoperative radiotherapy methods included two-field irradiation (16 patients, 16.32%), four-field box irradiation (16 patients, 16.32%), and intensity-modulated radiotherapy (IMRT; 66 patients, 67.36%). The survival rates were represented using Kaplan-Meier curves, and prognosis analyses were performed using Cox multivariate analyses. RESULTS: The 5-year overall survival and progression-free survival rates were 82.0 and 76.0%, respectively. Only one patient (1.02%) developed a grade 3 acute radiation enteritis, while grade 3 and 4 myelosuppression was noted in 17 patients (17.35%) and one patient (1.02%), respectively. Multivariate analyses showed that anemia before radiotherapy and tumor size were predictors of the OS (P = 0.008, P = 0.045) rates. CONCLUSIONS: Postoperative radiotherapy for patients with risk factors of cervical cancer procured good efficacy levels with mild side effects. Anemia and tumor size were important OS predictors.

External validation and comparison of six prognostic models in a prospective cohort of HBV-ACLF in China.

UNLABELLED:  Background. Acute-on-chronic liver failure has high mortality. Currently, robust models for predicting the outcome of hepatitis B virus (HBV)-associated ACLF are lacking. AIM: To assess and compare the performance of six prevalent models for short- and longterm prognosis in patients with HBV-ACLF. MATERIAL AND METHODS: The model for end-stage liver disease (MELD), MELD sodium (MELD-Na), MELD to sodium ratio (MESO), integrated MELD, Child-Turcotte-Pugh (CTP), and modified CTP (mCTP) were validated in a prospective cohort of 232 HBV-ACLF patients. The six models were evaluated by determining discrimination, calibration and overall performance at 3 months and 5 years. RESULTS: According to the Hosmer-Lemeshow tests and calibration plots, all models could adequately describe the data except CTP at 3 months. Discrimination analysis showed that the iMELD score had the highest AUC of 0.76 with sensitivity of 62.6% and specificity of 80.2% for an optimal cut-off value of 52 at 3 months. It also had the highest AUC of 0.80 with sensitivity of 89.9% and specificity of 48.2% for an optimal cut-off value of 43 at 5 years. The overall performance of iMELD, assessed with Nagelkerke's R2 and the Brier score, was also the best among the six models. CONCLUSION: Integrated MELD may be the best model to predict short- and long-term prognosis in patients with HBV-ACLF.

Expression of HIF-1α and HIF-2α correlates to biological and clinical significance in papillary thyroid carcinoma.

BACKGROUND: The aim of this study was to detect the expression of hypoxia-inducible factor (HIF)-1α and HIF-2α in papillary thyroid carcinoma (PTC) compared with normal thyroid tissues. METHODS: The mRNA levels and protein levels of HIF-1α and HIF-2α were detected by real-time PCR and Western blot separately in 30 pairs of PTCs and normal thyroid cases. The protein levels were also detected by immunohistochemistry (IHC) using 92 samples of PTC group and 46 normal samples as control group for analyzing the biological and clinical significance of the expression of HIF-1α/HIF-2α. RESULTS: Real-time PCR results showed the mRNA level of HIF-1α and HIF-2α were significantly higher in PTC than normal group (P<0.001). Also, significantly higher positive rates (73%/65%) of HIF-1α and HIF-2α were observed in PTC compared with the control group (27%/35%) by IHC (P<0.01); the consistent results were gotten with Western blot. Although we did not find a significant correlation between the expression of HIF-1α and HIF-2α with gender, age, calcification, or Hashimoto's disease in the present study (P>0.05), both of their expressions were correlated to lymph node metastasis (P<0.05), capsular invasion (P<0.05), and TNM stage (P<0.05). CONCLUSIONS: Overexpression of HIF-1α and HIF-2α are associated with the carcinogenesis of PTC, served as potential biomarkers of PTC.

Logistic regression model can reduce unnecessary artificial liver support in hepatitis B virus-associated acute-on-chronic liver failure: decision curve analysis.

BACKGROUND: Several models have been proposed to predict the short-term outcome of acute-on-chronic liver failure (ACLF) after treatment. We aimed to determine whether better decisions for artificial liver support system (ALSS) treatment could be made with a model than without, through decision curve analysis (DCA). METHODS: The medical profiles of a cohort of 232 patients with hepatitis B virus (HBV)-associated ACLF were retrospectively analyzed to explore the role of plasma prothrombin activity (PTA), model for end-stage liver disease (MELD) and logistic regression model (LRM) in identifying patients who could benefit from ALSS. The accuracy and reliability of PTA, MELD and LRM were evaluated with previously reported cutoffs. DCA was performed to evaluate the clinical role of these models in predicting the treatment outcome. RESULTS: With the cut-off value of 0.2, LRM had sensitivity of 92.6 %, specificity of 42.3 % and an area under the receiving operating characteristic curve (AUC) of 0.68, which showed superior discrimination over PTA and MELD. DCA revealed that the LRM-guided ALSS treatment was superior over other strategies including "treating all" and MELD-guided therapy, for the midrange threshold probabilities of 16 to 64 %. CONCLUSIONS: The use of LRM-guided ALSS treatment could increase both the accuracy and efficiency of this procedure, allowing the avoidance of unnecessary ALSS.

Local tumour progression after ultrasound-guided microwave ablation of liver malignancies: risk factors analysis of 2529 tumours.

OBJECTIVES: To identify the incidence and risk factors that predict local tumour progression (LTP) after ultrasound-guided percutaneous microwave ablation (MWA) of liver malignancies. MATERIALS AND METHODS: One thousand two hundred and nine patients with 2,529 malignant nodules (mean size 2.8 ± 1.4 cm, range 0.9-8.0 cm) were treated by MWA between July 2005 and December 2012. The influence of 11 factors on the risk of LTP was assessed. Univariate Kaplan-Meier and Cox proportional hazard models were used for statistical analysis. RESULTS: The overall LTP was 4.2 % per tumour and 8.6 % per patient with a median follow-up of 20.3 months. LTP per tumour was 4.3 % for primary liver cancer and 4.1 % for metastases (p = 0.32). The survival of LTP and free-LTP patients at 1, 3, and 5 years was 92.4 %, 71.6 %, and 45.1 %, respectively, and 92.9 %, 70.1 %, and 52.4 %, respectively (p = 0.93). By univariate analysis, tumour location, size and ablation time were significant risk factors of LTP. Multivariate analysis identified tumour size (>3.0 cm) to be the only independent predictor of LTP. CONCLUSIONS: MWA of liver malignancies achieves a relatively low-incidence LTP, although LTP risk significantly increases if tumour size >3.0 cm. The technique seems to be appropriate even for patients with a tumour at a risk location. KEY POINTS: • Microwave ablation of liver malignancies achieves a low incidence local tumour progression. • LTP risk significantly increases if the tumour size is >3.0 cm. • MWA seems to be appropriate even for patients with a tumour at a risk location.

Identifying patients with chronic hepatitis B at high risk of type 2 diabetes mellitus: a cross-sectional study with pair-matched controls.

BACKGROUND: The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients. METHODS: A cross-sectional study with pair-matched controls was conducted in Nantong Third People's Hospital, Nantong University, China. From January 2008 to December 2012, a total of 1783 CHB patients were screened for study subjects, among whom 207 patients with T2DM were enrolled as cases and 207 sex- and age-matched non-DM patients as controls. Demographic, anthropometric, lifestyle, clinical, and laboratory data were obtained from each subject. RESULTS: In the univariate model, thirteen variables showed marked differences between the DM group and non-DM group. Patients with longer duration of CHB (≥15 years) and alcoholic steatosis showed the highest likelihood of T2DM (odds ratio = 5.39 and 4.95; 95% confidence intervals 2.76-10.53 and 1.65-14.91). In the multivariate adjusted analysis, three CHB-related factors, namely high viral load, long duration of illness, and presence of cirrhosis, contributed to substantially increase the likelihood of T2DM, in addition to the other five risk factors including family history of DM, low education level, elevated triglycerides (TG), gamma-glutamyl transferase (GGT) levels, and presence of alcoholic steatosis. CONCLUSIONS: Our findings suggest that high viral load, long duration of CHB, presence of cirrhosis, alcoholic steatosis and several other factors may be potential risk factors for development of T2DM in CHB patients. It is of vital importance to monitor glucose in high-risk CHB patients and aggressively intervene on modifiable risk factors.

Hepatitis B virus infection status and risk of type 2 diabetes mellitus: A meta-analysis.

AIM: Whether hepatitis B virus (HBV) infection increases the risk of type 2 diabetes mellitus (T2DM) is controversial. We carried out a meta-analysis to evaluate the association between HBV infection status and the risk of T2DM. METHODS: The PubMed, Embase and Ovid databases were searched for relevant studies on an association between HBV infection and the risk of diabetes. Methodological quality was assessed using the adapted Newcastle-Ottawa Quality Assessment Scale. A fix- or random-effects model was used to summarize odd ratios (OR) and 95% confidence intervals (CI). RESULTS: We included seven cohort studies, four case-control and four cross-sectional studies, involving 118 530 participants. The prevalence of T2DM differs by HBV infection status. Pooled estimators indicated a nearly twofold excess T2DM risk with hepatitis B cirrhosis (HBC) status. The summary OR of the risk of T2DM for HBC patients was 1.99 (95% CI, 1.08-3.65) when compared with the non-HBV individuals, and 1.74 (95% CI, 1.43-2.13) when compared with non-cirrhotic chronic hepatitis B (NC-CHB) patients. In contrast, no significant correlation was found between asymptomatic HBV carriers or NC-CHB patients and the incidence of diabetes, compared with non-HBV controls. CONCLUSION: Our findings suggest that while HBV itself may not be pro-diabetic, the HBV-derived cirrhosis is an independent risk factor for T2DM.

Orally administered moxifloxacin prolongs QTc in healthy Chinese volunteers: a randomized, single-blind, crossover study.

AIM: To investigate the QT/QTc effects of orally administered moxifloxacin in healthy Chinese volunteers. METHODS: This was a single-blinded, randomized, single-dose, placebo-controlled, two-period cross-over study. A total of 24 healthy Chinese volunteers were enrolled, randomly assigned to two groups: one group received moxifloxacin (400 mg, po) followed by placebo with a 7-d interval, another group received placebo followed by moxifloxacin with a 7-d interval. On the days of dosing, 12-lead 24 h Holter ECGs were recorded and evaluated by an ECG laboratory blind to the treatments. Blood samples were collected to determine plasma concentrations of moxifloxacin. RESULTS: The orally administered moxifloxacin significantly prolonged the mean QTc at all time points except 0.5 h post-dose. The largest time-matched difference in the QTcI was 8.35 ms (90% CI: 5.43, 11.27) at 4 h post-dose. The peak effect on QTcF was 9.35 ms (90% CI: 6.36, 12.34) at 3 h post-dose. A pharmacokinetic-QTc model suggested a 2.084 ms increase in the QTc interval for every 1000 ng/mL increase in plasma concentration of moxifloxacin. In addition, the orally administered moxifloxacin was well tolerated by the subjects. CONCLUSION: Orally administered moxifloxacin significantly prolongs QTc, which supports its use as a positive control in ICH-E14 TQT studies in Chinese volunteers.

[Involvement of the receptor component protein in the regulation of vascular peroxidase-1 expression induced by calcitonin gene-related peptide and angiotensin II in vascular smooth muscle cell].

Angiotensin II (Ang II) and calcitonin gene-related peptide (CGRP) play important roles in vascular injury and protection. In order to determine the role of CGRP receptor component protein (RCP) in signal transduction whereby CGRP and Ang II mediate the expression of vascular peroxidase-1 (VPO1) in vascular smooth muscle cell (VSMC), mouse derived A10 vascular smooth muscle cell line (A10VSMC) was cultured with CGRP or/and Ang II in vitro. RCP-specific small interference RNA (siRNA-RCP) was used to silence oligonucleotide sequence. Western blot and RT-PCR were used to determine the protein and mRNA expressions of RCP and VPO1, respectively. The results showed that the expressions of RCP and VPO1 were increased in the presence of CGRP or Ang II in the quiescent A10VSMC. But the protein expressions of RCP and VPO1 induced by Ang II were decreased by pretreatment of CGRP (P < 0.05). The expressions of VPO1 were decreased in all the groups treated with siRNA-RCP, compared with those of wide-type counterparts. Meanwhile, the expression of VPO1 was significantly induced by CGRP but not Ang II in the siRNA-RCP treated A10VSMCs. Ang II in combination with CGRP increased the protein expression of VPO1 in the siRNA-RCP-transfected cells, compared with Ang II alone, and this effect could be abolished by catalase. The results suggest that RCP may play an important role in the integration of signal transduction whereby CGRP and Ang II receptors jointly regulate VPO1 expression in VSMC.