Objective To investigate the characteristics and risk factors of thyroid dysfunction induced after interferon therapy in patients with chronic viral hepatitis.Methods The clinical data of 96 chronic viral hepatitis patients received interferon therapy were analyzed retrospectively.Serological markers of thyroid function and thyroid autoantibodies changes were observed,and were followed up for 1 year after treatment.Logistic regression analysis was performed to evaluate risk factors of thyroid dysfunction.Results Among the 96 cases,84 cases didn't develop thyroid dysfunction after interferon therapy(normal group),and 12 cases developed thyroid dysfunction after interferon therapy (abnormal group),the incidence was 12.5％ (12/96),there were 5 cases of Hashimoto's thyroiditis,3 cases of Graves disease,3 cases of destructive thyroiditis,and 1 case of non-autoimmune hypothyroidism.The time to develop thyroid dysfunction was 2-7 (3.8 ± 1.9) months after treatment,the duration of thyroid dysfunction was 1-11 (4.2 ± 0.9) months.Five patients received endocrine therapy,and 2 patients stopped interferon therapy.All patients regained normal thyroid function during 1-year followup after end of treatment.Multivariate Logistic regression analysis showed that female gender (OR =3.767) and anti-thyroid peroxidase antibodies (OR =1.117) were the independent risk factors for thyoid dysfunction.Conclusions Hashimoto's thyroiditis,Graves disease,destructive thyroiditis and non-autoimmune hypothyroidism are the main types of thyroid dysfunction induced after interferon therapy in patients with chronic viral hepatitis.The thyroid function and thyroid autoantibodies should be closely monitored during treatment in patients with chronic viral hepatitis receiving interferon therapy,especially in female and patients who have thyroid autoantibodies.

Objective To observe the efficacy and safety of peginterferon α-2a and entecavir treatment in chronic hepatitis B(CHB)patients with alanine aminotransferase(ALT)＜2×upper limit of normal(ULN)and hepatic inflammatory activity(G)≥2.Methods 0ne hundred CHB patients with ALT＜2×ULN and G≥2 were enrolled in the open-label and control study. Fifty patients were treated with peginterferon α-2a including 34 hepatitis B e antigen(HBeAg)positive cases and the other 50 patients were treated with entecavir including 33 HBeAg positive cases.The patients were evaluated at week 48 of treatment. The data were analyzed using variance test,t test,Wileoxon test and X~2 test. Results Baseline levels of hepatitis B virus(HBV)DNA,ALT, HBeAg, hepatitis B surface antigen(HBsAg)and hepatic histology were comparable in peginterferon a-2a group and entecavir group. At week 48 of treatment, HBV DNA negative rates in the 2 groups were 66.0% and 72.0%,respectively(X~2=0.421,P=0.517);HBV DNA levels decreased(3.08±1.43)lg copy/mL and(3.79±1.36)lg copy/mL, respectively(t=2.544,P=0.013).Five(10%)patients in peginterferon α-2a group achieved HBsAg loss, while only 1(2.0%)in entecavir group(X~2=2.837,P=0.204);three(6%)patients in peginterferon α-2a group achieved HBsAg seroconversion, while no one in entecavir group(X~2=3.093,P=0.242).Fourteen(41.2%)HBeAg positive patients in peginterferon α-2a group achieved HBeAg loss and seroconversion,while 5(15.2%)HBeAg positive patients in entecavir group achieved HBeAg loss and 4 of them(12.1%)obtained HBeAg seroconversion (X~2=5.583,P=0.018;X~2=7.159,P=0.007).Paired liver biopsies before and after treatment were done in 15 patients in peginterferon α-2a group and 14 in entecavir group. Eleven patients in peginterferon α-2a group and 9 in entecavir group achieved necroinflammatory improvement(Knodell score decline ≥2)at week 48 of treatment(X~2=0.277,P=0.599).Concusions CHB patients with ALT＜2×ULN and G≥2 treated with peginterferon α-2a could achieve virological response,serological response and histologic improvement with good safety. HBeAg seroconversion rate in patients treated with pegintert'eron α-2a is much higher than that in patients treated with entecavir.

Objective To compare the efficacy of peginterferon (Peg-IFN) α-2a in HBeAg positive chronic hepatitis B (CHB) patients with mildly elevated alanine aminotransferase (ALT) level [ALT＜2× upper limit of normal (ULN)] and active hepatic inflammation(G≥2).Methods Fiftyfive HBeAg positive CHB patients with mildly elevated ALT (＜2×ULN) and active hepatic inflammation (G≥2) were enrolled in this randomized,open-label,controlled study.These patients were treated with either Peg-IFN α-2a 180 μg once weekly (n=27) or entecavir 0.5 mg once daily (n=28) for 48 weeks.The data were analyzed using chi-square test and t test.Results After 24 weeks of treatment,8 cases (29.6%) achieved HBeAg loss and 6 cases (22.2%) achieved HBeAg seroconversion in Peg-IFN α-2a group while none in entecavir group (χ2=9.71,P＜0.01;χ2=6.98,P＜0.0 1).Besides,two patients (7.4%) in Peg-IFN α-2a group achieved HBsAg loss.Compared with baseline level,the mean HBeAg titer at week 24 decreased (1 179.8±582.6) PEIU/mL in Peg-IFN α-2a group and (441.5±258.8) PEIU/mL in entecavir group (t=2.66,P=0.01),respectively.At week 24,the serum HBV DNA reduction in entecavir group was more dramatic than that in Peg-IFN α-2a group [(4.520±0.694) lg copy/mL vs.(3.520±1.442) lg copy/mL,t=2.45,P=0.029].In PegIFN α-2a group,the rate of HBeAg loss in patients with G=3 was higher than that in patients with G=2 (χ2=4.23,P=0.041).Conclusions Twenty-four-week treatment with Peg-IFN α-2a is more effective in term of HBeAg loss,HBeAg seroconversion and HBeAg titer reduction than entecavir,while entecavir is more effective in term of serum HBV DNA reduction.Patients with higher baseline hepatic inflammatory activity scores are more possible to achieve HBeAg loss when treated with Peg-IFN α-2a.

ObjectiveTo investigate the factors influencing the liver histological features in chronic hepatitis B virus (HBV) infection patients with low alanine transaminase (ALT) levels by analyzing the relationship of serum hepatitis B surface antigen (HBsAg) level with liver inflammation grade and fibrosis stage. MethodsA total of 511 HBV infection patients admitted to our hospital from December 2010 to December 2013 were studied. The liver histological features, serum HBsAg level, and HBV DNA copy number were examined. Comparison of categorical data between different groups was made by chi-square test, comparison of continuous data following the normal distribution was made by t test, and comparison of continuous data not following the normal distribution was made by Kruskal-Wallis H test. The relationship of serum HBsAg level with liver inflammation grade and fibrosis stage was determined by Spearman′s rank correlation analysis. ResultsAll patients showed different degrees of hepatic histological abnormalities. The group aged more than or equal to 40 years had significantly lower HBeAg positive rate, HBsAg level, and HBV DNA copy number compared with the group aged less than 40 years (χ2=86.8, P＜0000 1; t=2.99, P=0.003; t=7.25, P＜0.000 1). The groups with different ages had significant differences in liver inflammation grade and fibrosis stage (χ2=70.03, P＜0.000 1; χ2=61.92, P＜0.000 1). The Spearman′s rank correlation analysis indicated that in both HBeAg-positive and -negative patients HBsAg level was negatively correlated with liver inflammation grade (r=-0.245, P＜0.000 1; r=-1.51, P=0019) and fibrosis stage (r=-0.153, P=0.012; r=-0.181, P=0.005). ConclusionAge is one of the important factors influencing the liver histological progression in chronic HBV infection patients with low ALT levels. HBsAg level is negatively correlated with liver inflammation grade and fibrosis stage in chronic HBV infection patients with low ALT levels, so it could be used as an important non-invasive indicator for the liver histological status in these patients.

Objective: To investigate the clinical effect of 156-week telbivudine sequential therapy in HBeAg-positive chronic hepatitis B patients with suboptimal response to pegylated interferon-α-2a (Peg-IFN-α-2a) therapy. Methods: A total of 35 HBeAg-positive CHB patients with HBV DNA < 500 IU/ml who were treated with Peg-IFN-α-2a for 48 weeks and did not experience seroconversion of HBeAg were given telbivudine sequential therapy for 156 weeks. HBeAg clearance rate, HBeAg seroconversion rate, HBV DNA clearance rate, safety, and drug resistance rate were analyzed. The t-test was used for the analysis of continuous data and the chi-square test was used for the analysis of categorical data. A multivariate Cox regression analysis was used to identify the influencing factors for HBeAg seroconversion. Results: Telbivudine sequential therapy achieved an ideal HBeAg seroconversion rate of 87.88% with good tolerability and low drug resistance. The HBeAg clearance rate and HBeAg seroconversion rate increased over the time of treatment and were 45.45% and 45.45%, respectively, at 24 weeks and 93.94% and 87.88%, respectively, at 156 weeks. No patient had virologic breakthrough or HBsAg clearance during treatment. The multivariate Cox regression analysis showed that baseline HBsAg level (hazard ratio [HR] = 0.404, P = 0.003) and > 0.5 lg IU/ml reduction in HBeAg at 24 weeks (HR = 2.196, P = 0.048) were predictive factors for HBeAg seroconversion at 156 weeks. Conclusions In HBeAg-positive CHB patients with suboptimal response to Peg-IFN-α-2a therapy, 156-week telbivudine sequential therapy has a good clinical effect and can be used as an optimal regimen for such patients.

Objective: To investigate the optimal treatment regimen for patients with HBeAg-positive chronic hepatitis B (CHB) after suboptimal response to 24 weeks of pegylated interferon (Peg-IFN) α-2a. Methods: A total of 188 patients with HBeAg-positive CHB who had suboptimal response to 24 weeks of Peg-IFN α-2a were randomly divided into entecavir group (n = 93) and telbivudine group (n = 95). The two groups received entecavir 0.5 mg/d and telbivudine 0.6 g/d, respectively, for 208 weeks. After 208 weeks of treatment, the following indices were assessed: HBeAg clearance rate and seroconversion rate, hepatitis B virus (HBV) DNA clearance rate (HBV DNA < 500 IU/ml), safety, and drug resistance rate. The data were subjected to intention-to-treat (ITT) analysis and per protocol (PP) analysis. Univariate and multivariate logistic regression analyses were performed for the drugs used and baseline characteristics in patients with or without HBeAg seroconversion, and stratification analysis was performed based on the baseline HBeAg level. Results: Six cases in the entecavir group and four cases in the telbivudine group did not complete the treatment. Sequential entecavir and telbivudine were well tolerated and safe for all patients. There was a significant difference in HBV DNA clearance rate at 52 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 93.55% [87/93] vs 77.89% [74/95], χ ² = 9.363, P = 0.002; PP analysis: 93.10% [81/87] vs 76.92% [70/91], χ ² = 9.049, P = 0.003). The suppression rates of HBV DNA at 208 weeks of treatment were 95.70% (89/93) vs 92.63% (88/95) (ITT analysis) and 95.40% (83/87) vs 92.31% (84/91) (PP analysis). There was a significant difference in HBeAg seroconversion rate at 208 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 38.71% [36/93] vs 62.11% [59/95], χ ² = 10.290, P = 0.001; PP analysis: 41.38% [36/87] vs 64.84% [59/91], χ ² = 9.833, P = 0.002). Univariate and multivariate logistic regression analyses suggested that sequential use of telbivudine, male sex, and the baseline level of HBeAg were significantly associated with HBeAg seroconversion at 208 weeks of treatment (P = 0.003, hazard ratio [HR] = 0.386; P = 0.009, HR = 0.303; P = 0.001, HR = 3.502). Conclusion For patients with HBeAg-positive CHB after suboptimal response to 24 weeks of Peg-IFNα-2a, sequential use of telbivudine is the optimal treatment regimen according to the baseline level of HBeAg (baseline guidance). The incidence of HBeAg seroconversion during 208 weeks of sequential treatment can be significantly increased according to the HBeAg decline curve in early treatment (24 weeks) and 104 weeks (response guidance).

Chronic hepatitis B caused by hepatitis B virus (HBV) infection is a global public health issue. Antiviral therapy for chronic HBV infection plays a critical role, and the goal of antiviral therapy is mainly defined by virological, serological, and biochemical parameters. As the two types of antiviral drugs approved for marketing, both interferon and nucleos(t)ide analogues can alleviate liver inflammation and liver fibrosis and reduce the incidence rates of liver cirrhosis and hepatocellular carcinoma. However, the ideal goal of antiviral therapy is functional cure, which significantly improves the long-term outcome of chronic hepatitis B. The limitation of current treatment is that it can inhibit HBV replication, but cannot clear the virus, with low serological clearance rates of HBeAg and HBsAg. Development of new drugs with the goal of functional cure and evaluation of the synergistic and combined effects of existing drugs are important directions for HBV treatment and development.

Objective To investigate analgesic effects of the selective blocking of descending facilitation targeting μ opioid receptor positive neurons in the rostral ventromedial medulla ( RVM) in a rat model of bone cancer pain. Methods Forty-eight adult female Wistar rats weighing 180-200 g were randomly divided into 6 groups: group Ⅰ control ( n = 3) ;group Ⅱ bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells ( n = 9) ;group Ⅲ-Ⅵ received a single intra-RVM micro-injection of PBS (group Ⅲ), dermorphin (group Ⅳ) , saporin (group Ⅴ) and dermorphin-saporin ( group Ⅵ) respectively at 28 days before intra-tibia inoculation ( n = 9 each) . Starting from 3 to 20 days after intra-tibia inoculation, mechanical allodynia was assessed and recorded. The animals were sacrificed on 7, 14 and 20 days after intra-tibia inoculation, after repetitive non-noxious tactile stimulation of the hindpaw. The total number of Fos-positive neurons in the spinal dorsal horn was measured as a marker indicative of central sensitization. Results The animals developed nociceptive hypersensitivity after intra-tibia cancer cell inoculation in group Ⅱ -Ⅵ . Nociceptive hypersensitivity was significantly decreased during 4-7 days after the onset of nociception in group Ⅵ (dermorphin-saporin). The number of Fos positive neurons in bilateral spinal dorsal horn was significantly increased by intra-tibia inoculation of cancer cells in group Ⅱ-Ⅵ as compared with control group and was significantly lower at day 14 and 20 after inoculation in group Ⅵ (dermorphin-saporin) than in group Ⅱ - Ⅴ.Conclusion Selective blocking of descending facilitation targeting μ opioid receptor positive neurons in RVM can effectively reduce nociceptive hypersensitivity induced by intra-tibia inoculation of Walker56 mammary gland carcinoma cells.

OBJECTIVETo investigate the efficacy of anti-hepatitis B virus (HBV) drugs for preventing vertical transmission of HBV and the safety of these drugs when given as treatment during pregnancy (to women) or insemination (to men).

METHODSCases of women and men who had taken anti-HBV drug therapy during pregnancy or insemination, respectively, were retrospectively selected for study from among 18 hospitals and 33 specialists in the Guangdong Province. Demographic, HBV infection and treatment data was collected for puerperal men or women and their newborns from the medical records.

RESULTSA total of 122 cases with detailed follow-up data were included in the study and including 74 women who were administered lamivudine (LAM) more than telbivudine (LdT) more than adefovir (ADV)more than entecavir (ETV) (hierarchy ranking by number of cases) and 48 men who were administered LAM more than ADV more than LdT more than ETV.None of the 122 newborns related to these cases showed HBV infection at 7 months of follow-up.None of the 74 puerperal women showed complications related to reproduction.There was one ease of a newborn being underweight at birth (2.1 kg), for which the mother had taken LdT during pregnancy. There was also one case of a newborn with a harelip and one case of a newborn with an inguinal hernia, for which both of the fathers had taken ADV during the time of insemination.

CONCLUSIONThis retrospective investigation carried out in Guangdong Province indicated that not only are anti-HBV drugs efficacious for blocking vertical transmission of HBV but also are safe for both mothers and infants when taken by fathers or mothers during the reproduction phases of insemination and pregnancy.

Adenine ; analogs & derivatives ; Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Guanine ; analogs & derivatives ; Hepatitis B ; drug therapy ; Hepatitis B virus ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Lamivudine ; Male ; Mothers ; Organophosphonates ; Pregnancy ; Retrospective Studies ; Thymidine ; analogs & derivatives ; Time Factors

Grape (Vitis vinifera L.) in production is frequently exposed to inadequate light, which significantly affects its agronomic traits via inhibiting their physiological, metabolic and developmental processes. To explore the mechanism how the grape plants respond to the weak light stress, we used 'Yinhong' grape and examined their physiology-biochemistry characteristics and transcriptional profile under different levels of weak light stress. The results showed that grape seedlings upon low intensity shading treatments were not significantly affected. As the shading stress intensity was strengthened, the epidermis cells, palisade tissue, and spongy tissue in the leaves were thinner, the intercellular space between the palisade tissue and spongy tissue was larger compared with that of the control, and the activities of superoxide dismutase, catalase and peroxidase were decreased gradually. Additionally, the soluble protein content increased and the free proline content decreased gradually. Compared with the control, significant changes in plant photosynthetic characteristics and physiology-biochemistry characteristics were observed under high intensity of shading (80%). RNA-seq data showed that the differentially expressed genes between CK and T2, CK and T4, T2 and T4 were 13 913, 13 293 and 14 943, respectively. Most of the enrichment pathways were closely related with the plant's response to stress. Several signaling pathways in response to stress-resistance, e.g. JA/MYC2 pathway and MAPK signal pathway, were activated under weak light stress. The expression level of a variety of genes related to antioxidation (such as polyphenol oxidase and thioredoxin), photosynthesis (such as phytochrome) was altered under weak light stress, indicating that 'Yinhong' grape may activate the antioxidation related pathways to cope with reactive oxygen species (ROS). In addition, it may activate the expression of photosynthetic pigment and light reaction structural protein to maintain the photosynthesis activity. This research may help better understand the relevant physiological response mechanism and facilitate cultivation of grape seedlings under weak light.
Vitis/metabolism* ; Gene Expression Regulation, Plant ; Photosynthesis/genetics* ; Plant Leaves ; Light ; Seedlings/metabolism*