Bushen Jianpi Formula Combined with Entecavir for the Treatment of HBeAg-Negative Chronic Hepatitis B: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Bushen Jianpi formula (BSJPF, also known as Lingmao formula) is a traditional Chinese medicine for chronic hepatitis B (CHB). The previous study has suggested that the treatment combination of BSJPF and entecavir (ETV) can achieve a significant loss of hepatitis B e antigen (HBeAg) and a significant decrease in serum level of hepatitis B virus (HBV) DNA in HBeAg-positive CHB patients with mildly elevated alanine aminotransferase. Objective: This study aimed to evaluate the efficacy and safety of BSJPF combined with ETV for treating HBeAg-negative CHB patients. Methods: A total of 640 patients were assigned randomly to the treatment group (receiving BSJPF combined with ETV for 96 weeks) or the control group (receiving a placebo combined with ETV for 96 weeks) in a 1 : 1 ratio. The primary endpoints are the rate of loss of hepatitis B surface antigen (HBsAg). The secondary outcomes included the rate of decrease in the HBsAg concentration to ≥1 lg·IU/mL, the HBV DNA suppression, the decline of the level of covalently closed circular DNA (cccDNA) in the liver, histological improvements, and the rate of ALT normalization. Results: The rate of HBsAg loss in the treatment group was significantly higher than that of the control group (5.5% versus 1.8%, P=0.031). There were 11.1% of patients in the treatment group who recorded a reduction in HBsAg ≥1 lg·IU/mL, which is better than 5.9% of patients in the control group (P=0.043). There was no significant difference between the two groups with regard to the rate of HBV DNA clearance, the reduction in intrahepatic cccDNA, and the rate of ALT normalization (P > 0.05). The rate of liver fibrosis improvement in the treatment group was better than that of the control group (35.5% versus 11.8%, P=0.031), but there was no difference in necroinflammatory improvement (P > 0.05). The adverse events (AEs) were similar between the two groups, except for the abnormal kidney function, with 2.2% in the control group and 0.0% in the treatment group (P=0.028). Conclusion: The combination of BSJPF and ETV can increase the rate of HBsAg loss and the rate of histological fibrosis improvement without serious adverse events in CHB patients. Trial Registration. This trial is registered with ChiCTR-IOR-16009880 on November 16, 2016-retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=16836.

Histopathological and molecular insights into the ovicidal activities of two entomopathogenic fungi against two-spotted spider mite.

Entomopathogenic fungi can infect and kill spider mite eggs but their ovicidal activities are poorly understood. Here we gain histopathogenical and molecular insights into the ovicidal activities of Beauveria bassiana and Isaria fumosorosea against the two-spotted spider mite, Tetranychus urticae. Scanning electronic microscopy indicated successful adhesion and germination of fungal conidia on egg shell at 24h post-spray (HPS). Germ tubes of both fungi could penetrate into egg shell with penetration pegs at 48 HPS. Interestingly, the germ tubes of B. bassiana may elongate on egg surface to locate appropriate sites for penetration, acting as 'searching' hyphae. Aside from the normal penetration, the germ tubes of I. fumosorosea can be completely or partially embedded into egg shell for a distance of extension, forming shell humps. Light microscopy of ultrathin sections of infected eggs showed shrunken (affected) or disrupted embryos at 48-96 HPS despite little effect on egg cleavage at 24 HPS. However, distinguishable hyphal cells were hardly found inside the embryos lacking oxygen although fungal outgrowths were abundant on unhatched (killed) eggs. In PCR with specific probes, the 18S rDNA signals of B. bassiana (412 bp) and I. fumosorosea (454 bp) in the DNA extracts from surface-cleaned mite eggs increased at 0-96 HPS, confirming fungal colonization in the infected eggs. We consider that the colonization on shell surface and underside could rely upon extending hyphae for uptake of egg nutrition, resulting in embryo disruption. Our observations add knowledge to microbial control of spider mites.

Effect of fungal infection on reproductive potential and survival time of Tetranychus urticae (Acari: Tetranychidae).

The effect of fungal infection on the reproductive potential of two-spotted spider mite, Tetranychus urticae, was evaluated as part of the full biocontrol potential of three entomopathogenic fungi by modeling of fecundity probability. Female mites (or= 0.98), yielding a solution to the probability for the female mites to achieve a specific fecundity {P(m 10 eggs despite some variation among the tested fungi. In contrast, the chances for the non-infected mites to achieve the low and high fecundities were 23 and 55%. The fitted probabilities provide a full coverage of the fecundity potential of infected versus non-infected mites and are more informative than the mean fecundities.

Sprays of emulsifiable Beauveria bassiana formulation are ovicidal towards Tetranychus urticae (Acari: Tetranychidae) at various regimes of temperature and humidity.

Aerial conidia of Beauveria bassiana in an emulsifiable formulation germinated by >95% after 24 h exposure to the regimes of 20, 25 and 30 degrees C with 51%, 74% and 95% RH. Ovicidal activities of the formulation towards two-spotted spider mite, Tetranychus urticae, were assayed at the concentrations of 0, 18, 160 and 693 conidia mm(-2) sprayed separately onto fava bean leaves including 39 (25-76) eggs per capita. All the sprayed eggs on the leaves were directly exposed to the different regimes for hatch after 24 h maintenance in covered Petri dishes. Generally, hatched proportions increased over post-spray days and decreased with the elevated fungal concentrations; no more eggs hatched from day 9 or 10 onwards. Based on the counts of the hatched/non-hatched eggs in the different regimes, the final egg mortalities were 15.0-40.4%, 48.9-66.6% and 62.9-87.5% at the low, medium and high concentrations, respectively, but only 5.6-11.3% in blank controls. The RH effect on the fungal action was significant at 20 and 25 degrees C but not at 30 degrees C whereas the effect of temperature was significant at 51% and 74% RH but not at 95% RH. Probit analysis of the egg mortalities versus the fungal sprays generated median lethal concentrations (LC(50)) of 65-320 conidia mm(-2) at all the regimes, and of only 65-78 conidia mm(-2) at 25-30 degrees C with 74-95% RH. The results highlight ovicidal activities of the emulsifiable formulation against the mite species at the tested regimes and its potential use in spider mite control.

WB1106, a novel nitric oxide-releasing derivative of telmisartan, inhibits hypertension and improves glucose metabolism in rats.

Angiotensin converting enzyme (ACE) inhibitors usually cause severe coughing and intolerance while antagonists for angiotensin AT(1) receptor do not stimulate the production of nitric oxide (NO). NO has been shown to regulate arterial hypertension and insulin resistance. Hence, new hybrids of antagonist for angiotensin AT(1) receptor and a NO donor may have potent anti-hypertensive effect and regulate glucose metabolism and insulin resistance. Herein, the effects of [6-(nitrooxymethyl)pyridin-2-yl] methyl 4'-[1-(1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzo[d]imidazol-3'-yl)ethyl] biphenyl-2-carboxylate (WB1106), a novel NO-releasing derivative of telmisartan newly synthesized, on the vasocontraction, hypertension and diet-induced insulin resistance were examined in vitro using rat aortic strips and in normotensive and spontaneous hypertension rats (SHR rats). Apparently, WB1106 induced the vasorelaxation of contracted rat aortic strips in a dose- and time-dependent manner, which depended on the activity of guanylate cyclase, a characteristic of NO-related function. Furthermore, WB1106 reduced the contractile and blood pressure responses to angiotensin II, which relied on the release of telmisartan. Moreover, treatment with WB1106 significantly reduced the blood pressure with similar potency to telmitarsan and increased the contents of cGMP in SHR rats. Therefore, WB1106 possesses both the angiotensin AT(1) receptor antagonist activity of telmisartan and the NO-releasing property of a 'slow NO donor'. Importantly, in contrast to equimolar telmisartan, treatment with WB1106 significantly attenuated body weight gains and improved glucose tolerance in high-fat and carbohydrate-fed rats, reflecting a synergistic effect of NO and telmisartan. Potentially, WB1106 may be a potent anti-hypertensive drug for treatment of hypertension and diabetes-related cardiovascular diseases in the clinic.

MR dynamic Gadolinium-enhanced fast multiplanar spoiled gradient-echo and spin-echo T1-weighted fat-suppressed techniques in diagnosis of pancreatic carcinoma.

OBJECTIVE: To evaluate the value of MR dynamic Gadolinium-enhanced fast multiplanar spoiled gradient-echo (FMPSPGR) and spin-echo (SE) T1-weighted fat-suppressed techniques in the diagnosis of pancreatic carcinoma. METHODS: Eighteen cases of pancreatic carcinoma verified by surgical and pathologic results were examined by MR, and the MR sequences included SE T1WI, FSE T2WI, SE T1-weighted fat-suppressed and dynamic Gadolinium-enhanced FMPSPGR. RESULTS: Of 18 pancreatic carcinomas, 10, 6, and 2 tumors showed respectively hypo-intensity, iso-intensity and hyper-intensity on SE T1WI, meanwhile, 8, 6, and 4 tumors displayed hyper-intensity, iso-intensity and hypo-intensity on FSE T2WI in comparison with the normal pancreatic tissue. All of the tumors showed hypo-intensity on SE T1-weighted fat-suppressed and also obvious non-enhancement or slight enhancement on MR dynamic Gadolinium-enhanced FMPSPGR images during the arterial dominant phase scanning. CONCLUSION: SE T1-weighted fat-suppressed and MR dynamic Gadolinium-enhanced FMPSPGR sequences could evidently improve the sensitivity and specificity in the diagnosis of pancreatic carcinoma.