[A study of the clinical curative effect of nucleos(t)ide analogues treated to pegylated interferon-α add-on therapy in patients with chronic hepatitis B].

Objective: To investigate the hepatitis B surface antigen (HBsAg) clearance condition and its predictive factors after treatment with nucleos(t)ide analogues to pegylated interferon-α add-on therapy in patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who visited the First Affiliated Hospital of Zhengzhou University from 2018~2019 were prospectively enrolled. HBsAg≤ 1500 IU/mL, hepatitis B e antigen-negative, HBV DNA undetectable, received antiviral treatment with nucleos(t)ide analogues for at least one year, and pegylated interferon-α add-on therapy for 48 weeks were included. The primary endpoint of study was to determine the proportion of HBsAg clearance at 72 weeks. Concurrently, the predictive factors for HBsAg clearance were analyzed. Quantitative and qualitative data were analyzed using a t-test or non-parametric test and a Fisher's exact test. Results: A total of 38 cases were included in this study, of which 13 cases obtained HBsAg clearance at 48 weeks of therapy and another six cases obtained HBsAg clearance throughout the extended treatment period of 72 weeks, accounting for 50.00% of all enrolled patients. There was a significant difference in HBsAg dynamics between the HBsAg clearance group and the non-clearance group (P < 0.05). Univariate logistic regression analysis showed that patients' age, baseline, 12-and 24-week HBsAg levels, and early HBsAg reduction were predictive factors for HBsAg clearance at 72 weeks of treatment. Multivariate logistic regression analysis showed that age (OR = 1.311; P = 0.016; 95% confidence interval: 1.051~1.635) and HBsAg levels at 24 weeks of treatment (OR = 4.481; P = 0.004; 95% confidence interval: 1.634~12.290) were independent predictors for HBsAg clearance. Conclusion: Hepatitis B e antigen-negative, nucleos(t)ide analogue treated, HBsAg ≤ 1500 IU/mL, and HBV DNA undetectable, peg-IFNα add-on treatment for 48 weeks could promote HBsAg clearance in patients with chronic hepatitis B. Six of the sixteen cases (37.50%) who did not obtain HBsAg clearance at week 48 did so with the course of therapy extended to week 72. Hence, the optimal individualized treatment strategy should be customized according to the predictors rather than the fixed 48-week course. Age (≤ 38), baseline HBsAg level (≤2.86 log(10)IU/ml), HBsAg level at 24 weeks (≤ 0.92 log(10)IU/ml), and 12-week HBsAg decrease from baseline (≥ 0.67 log(10)IU/ml) indicate that patients are highly likely to obtain HBsAg clearance at the 72 weeks of combination therapy, in which the combined indicator based on HBsAg level ≤0.92 log(10)IU/ml at 24 weeks will identify 85.0% to 100.0% of patients with HBsAg clearance.

[Efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of OSAHS with soft palate oropharyngeal obstruction].

Objective: To explore the efficacy of relocation and expansion pharyngoplasty by suspension sutures in the treatment of obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Seventy-three patients(including 60 males and 13 females) with OSAHS admitted to the department of otorhinolaryngology of our hospital in recent two years were retrospectively analyzed. All the patients had velopharyngeal obstructionevaluated by electronic endoscopic Müller test and were divided into control group (34 cases) and observation group (39 cases). The patients in the control group were performed modified uvulopalatopharyngoplasty, while those in the observation group were performed relocation and expansion pharyngoplasty by suspension sutures.The scores of ESS, AHI and LSaO2 before and after treatment were collected and compared. Results: The total effective rate of the observation group was 94.87%, which was significantly higher than 79.41% of the control group. The AHI was lower and LSaO2 value was higher (χ2=-1. 896,-1. 968,P<0.05)in the observation group. The sleeping symptoms and quality of life of the two groups were significantly improved. The ESS score of the observation group was decreased more significantly than that of the control group after treatment, and the difference was statistically significant (χ2=-1.451,P<0.05). The incidence of foreign body sensation in pharynx of the observation group (89.74%) was higher than that of the control group (55.88%), and the postoperative bleeding and postoperative recurrence rate (0.00%, 2.56%) was lower than that of the control group (8.82%, 14.70%)with statistical significance (χ2=4.738,4.249,4.119,P<0.05).The incidence of transient nasopharyngeal reflux in both groups was low and statistically insignificant (χ2=0.629,P>0.05). Conclusions: Preoperative strict screening of indications plays an important role in the selection of palatopharyngeal surgery methods and curative effect. Relocation and expansion pharyngoplasty by suspension sutures can improve the clinical efficacy of OSAHS with better safety and less recurrence.

[Discussion on teaching reform of oral histopathology in multiple classes].

In the information age, teaching methods are undergoing tremendous changes, and the traditional teaching methods are difficult to draw students' attention. As the core course of stomatology, oral histopathology is an important foundation for oral students. Along with the rapid development of medical science, it is imperative to deepen the reform of teaching. This article discussed the diversified teaching methods conducted in oral histopathology course in Zhejiang University School of Stomatology in the past 10 years with the core teaching theory of "learning before teaching" including the exploration design course, case based learning, journal club, etc. Diversified teaching methods activated students' subjective initiative, which laid a foundation for the next stage of clinical study, and provided a guiding framework for the future teaching reforms.

Comparison of size-resolved hygroscopic growth factors of urban aerosol by different methods in Tianjin during a haze episode.

Size-resolved hygroscopic growth factors of urban aerosol during a haze episode were measured using a Humidified Tandem Differential Mobility Analyzer (HTDMA) (gm(RH)). These factors were also derived from size-resolved particulate chemical composition combined with the κ-Köhler theory (gκ(RH)) and the thermodynamic model ISORROPIA-II running in forward mode (giso-f(RH)) and reverse mode (giso-r(RH)), respectively. In terms of agreement among these hygroscopic growth factors, gκ(RH) matched gm(RH) best, followed by giso-r(RH). In contrast, giso-f(RH) demonstrated a poorer agreement with gm(RH). The good consistency among gm(RH), gκ(RH), and giso-r(RH) was because they only focus on the physical hygroscopic process, whereas giso-f(RH) contains not only the direct influence of relative humidity (RH) on particle size but also the influence of gaseous precursor on the particle chemical composition, which indirectly affects the hygroscopicity of the particles. In this sense, size-resolved gκ(RH) and giso-r(RH) in a wide size range are more adequate to investigate the impact of RH on light scattering and aerosol radiative forcing. At RH = 80%, gκ(RH) for accumulation mode particles was 1.30-1.45 on polluted days and higher than that on clean days (1.2-1.3). Whereas on both polluted and clean days, gκ(RH) of ultrafine and coarse mode particles were generally lower than 1.25. The strong hygroscopicity of accumulation mode particles observed on polluted days can deteriorate visibility due to their high extinction efficiency.

[Clinical features of 20 patients with phytosterolemia causing hematologic abnormalities].

Objective: To investigate the clinical and laboratory features of Phytosterolemia with hematological abnormalities. Methods: A retrospective study was performed on 20 patients with phytosterolemia admitted to the hematology department of the First Affiliated Hospital of Suzhou University during 2004-2017. History of patients was collected and the platelet counts, lipidomic analysis of plasma and osmotic fragility of erythrocytes were carried out. The erythrocyte and platelet morphology was examined by light microscope. Phytosterol levels in serum were measured by high performance liquid chromatography method. All of ABCG5/8 exons and intron-exon boundaries were amplified by PCR and directly sequenced to identify mutations. Results: All patients had been misdiagnosed as immune thrombocytopenia (ITP), or Evans syndrome with a mean delay of 21 years between symptom onset and accuracy diagnosis. The clinical manifestations of the patients were variable, but most of them presented with thrombocytopenia, anemia, splenomegaly from early ages, and xanthomas. Other major features were also observed, such as impaired liver functions (9 cases), premature atherosclerosis (5 cases) and/or arthritis (4 cases). Interestingly, all patients displayed an increased osmotic fragility of red cells and unique blood film features: large unequal platelets surrounded by a circle of vacuoles and various abnormal erythrocyte shapes, especially stomatocyte. Serum levels of the sitosterol and stigmasterol in the patients were remarkably elevated up to 331.05(276.00, 670.20)mg/L and 244.60(193.78,399.40)mg/L, about 10 and 24 times higher than those of normal subjects. There were 14 mutations in ABCG5/8 genes found in the patients. Among them, 2/3 of the mutations were in ABCG5 gene, including p.(E22X), p.(R446X),g.ISV7+3G>A, p.(R446X), p.(R419H), g.ISV7+3G>A, p.(G90E), p.(R389H) and g.7+2G>A), and 1/3 in ABCG8 gene involving p.(M614-K628del), p.(E25X), p.(L86P fs X185), p.(R263Q), p.(E500D fs X604) and p.(G674R) mutation. The ABCG5 p.(R446X) mutation was found in 3 separate families. Conclusions: The phenomena of thrombocytopenia/ stomatocyte/splenomegaly represents a special clinical manifestations of phytosterolemia, and distinct changes of blood cell morphology are the typical characters. Plasma plant sterols and ABCG5/ABCG8 genes should be analyzed when such hematologic abnormalities are unexplained.

[Studies on the role of chromobox protein homolog 2 in the inhibition of progression of hepatoma].

Objective: To explore chromobox protein homolog 2 (CBX2) expressions in relation to clinical features of patients and elucidate its role in the progression of hepatocellular carcinoma. Methods: Using the Cancer Genome Atlas (TCGA) database, R language was used to analyze the distribution of differentially expressed mRNA in hepatocellular carcinoma. The different expression of CBX2 in HCC and adjacent tissues and its relationship with survival and clinical characteristics of patients were further analyzed. The expression of CBX2 in liver tissues, liver cancer tissue, and L02, HepG2 and SMMC-7721 cell lines was detected by real time-PCR and western blot. The expression of CBX2 was interfered by siRNA in hepatoma cell line. MTT, colony formation, transwell assays, and flow cytometry were used to identify the proliferation, apoptosis, invasion and clone-formation ability of HepG2 and SMMC-7721 cells after CBX2 down-regulation. According to the different data, t-test, ANOVA, chi-square test, and COX regression model were used for statistical analysis. Survival curve was plotted through Kaplan-Meier method. Results: TCGA public database analysis showed that the expression of CBX2 mRNA in hepatocellular carcinoma tissues (7.296 ± 1.6115) was significantly higher than normal liver tissues (4.706 ± 0.940) (P = 0.000). In addition, the overall survival time of patients with low CBX2 mRNA expression was significantly longer than that of patients with high CBX2 mRNA expression [(5.971 ± 0.411) years vs. (4.650 ± 0.503) years, P = 0.001]. The expression level of CBX2 mRNA was correlated with the pathological TNM stage (P = 0.025) and differentiation degree (P < 0.001) of liver cancer. COX regression analysis showed that CBX2 mRNA expression was an independent predictor of patient survival (P = 0.013). siRNA was transfected and compared with the blank control group. The transgenic ability of HepG2 and SMMC-77221 cells decreased significantly at 72h (P < 0.05) and 96h (P < 0.05), and the apoptosis rate (11.430% ± 0.215%) was higher than blank control group (6.6 00% ± 0.170%) (P = 0.003). The number of invasive cells ((both P < 0.05) and relative colony forming cells ((both P < 0.001) were significantly decreased. In 20 cases of tissue samples, the expression of CBX2 protein (relative expression level 3.020 ± 0.269) in liver cancer was higher than that in adjacent tissues (relative expression level 0.886±0.065) (P < 0.001). The overall survival time of patients with low CBX2 expression in liver cancer was longer than that of patients with high expression [(3.670 + 0.576) years vs. (0.834 + 0.153) years, P = 0.004]. Conclusion: An evident high expression of CBX2 is an independent poor prognostic factor in hepatoma. Down-regulation of CBX2 expression can inhibit the progression of liver cancer. Therefore, CBX2 may be a prognostic biomarker and a new target for HCC treatment.

Down-regulation of telomerase reverse transcriptase-related anti-apoptotic function in a rat model of acrylamide induced neurobehavioral deficits.

Although the precise mechanism is unknown, neuron apoptosis is believed to participate in neuropathy caused by acrylamide (ACR). Telomerase reverse transcriptase (TERT) exhibits an anti-apoptotic function, but its contribution to the pathogenesis of ACR neurotoxicity is unclear. We investigated adult male rats that were given 30, 40 and 50 mg/kg ACR three times/week for 4 weeks. We found that ACR treatment caused significant deficits in sensory/motor function as measured by gait score, landing foot spread distance, movement initiation test and tail immersion test. Histological examination showed that the cerebral cortex in all ACR treated animals exhibited fewer neurons and more condensed nuclei than normal cortex. A significant increase in apoptosis was found in the cerebral cortex of rat brains subjected to ACR treatment in a dose-dependent manner. The expression of TERT in the brain was significantly reduced by ACR treatment. The pro-apoptotic cleaved caspase-3 protein level was increased, while the anti-apoptotic Bcl-2 protein level was decreased by 30 - 50 mg/kg ACR. Our findings indicate that TERT and its downstream regulators of neuron apoptosis, including Bcl-2 and cleaved caspase-3, were involved in ACR neurotoxicity.

Seasonal dynamics of the tick Haemaphysalis tibetensis in the Tibetan Plateau, China.

The tick Haemaphysalis tibetensis (Acari: Ixodidae) Hoogstraal is an important arthropod vector widespread in the Qinghai-Tibet Plateau, and knowledge of its seasonal dynamics is still poor. The current study investigated the seasonal dynamics of the parasitic and non-parasitic H. tibetensis over a 2-year period from March 2014 to February 2016 in the Tibetan Plateau, China. During this timeframe, non-parasitic ticks were collected weekly by flag-dragging in grassland and shrubland areas, and parasitic ticks were removed weekly from selected sheep. Plateau pikas were captured using traps and examined for immature ticks between May to September 2014. Results suggest that non-parasitic H. tibetensis were mainly distributed in the grassland, and the parasitic adults and nymphs were found mostly on sheep. Larvae were usually found on Plateau pikas and the prevalence of infestation and mean parasitic intensity were 72.1 and 1.81%, respectively. Adults were observed from March to July with the major peak occurring in mid-April. Nymphs were found from March to August and reached a peak in late June. Larvae were collected from April to September, and their numbers peaked in late May. In the parasitic and non-parasitic period, the overall sex ratio of males to females was 1.62 and 1.30, respectively. Results show that H. tibetensis can complete one generation per year, with a population overlap between stages over the spring-summer months. These findings provide additional information on the biology and ecology of H. tibetensis as well as insights on its control in the environment and on sheep.

[Effect of different concentrations of ammonium chloride on expression of hypoxia-inducible factor-1α in Chang liver cells].

Objective: To investigate the effect of treatment with different concentrations of ammonium chloride (NH4Cl) on the mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in Chang liver cells. Methods: Normal Chang liver cells were cultured and treated continuously with different concentrations of NH4Cl (1.25, 2.5, and 5 mmol/L). The Chang liver cells cultured normally were used as controls. RNA and protein were extracted at the 5th, 10th, and 15th generations. Quantitative real-time PCR, immunohistochemistry, and Western blot were used to measure the expression of HIF-1α and VEGF. Results: Quantitative real-time PCR showed that compared with the control group, the NH4Cl treatment group showed significant increases in the mRNA expression of HIF-1α and VEGF across the 5th, 10th, and 15th generations (F = 90976.659/1300.218/1896.800 and 41825.754/2381.321/2591.954, all P < 0.05). The results of immunohistochemistry showed that compared with the control group, the NH4Cl treatment group showed significant increases in the protein expression of HIF-1α and VEGF across the 5th, 10th, and 15th generations (F = 376.709/1615.358/1350.120 and 904.789/5105.186/8644.498, all P < 0.05). As was shown by the results of Western blot, compared with the control group, the NH4Cl treatment group showed significant increases in the protein expression of HIF-1α and VEGF across the 5th, 10th, and 15th generations (F = 228.499/6051.974/183.219 and 5549.429/40187.665/120982.183, all P < 0.05). Conclusion: Ammonia can increase the expression of HIF-1α and its downstream gene VEGF in Chang liver cells and cause the phenomenon of pseudohypoxemia.

[Acquired von Willebrand syndrome in three patients and literature review].

OBJECTIVE: To deepen the understanding of acquired von Willebrand syndrome (AVWS). METHODS: The clinical data of 3 patients were analyzed and related literature were reviewed. RESULTS: ① Case 1, a 70- year- old male, diagnosed as Waldenstrom macroglobulinemia and AVWS, was presented with spontaneous epitaxis and bruising. The VWF∶Ag level was 16%. Treatment was initiated with VWF concentrates. Two cycles of chemotherapy with Bortezomib, thalidomide and Dexamethasone were followed. Partial remission was achieved. Half- year' follow- up showed no sign of spontaneous hemorrhage. ② Case 2, a 48- year- old female, diagnosed as monoclonal gammopathy of undetermined significance and AVWS, was presented with repeated epitaxis. The VWF∶Ag level was 7%. Because the bleeding was slight and self-relieved, no specific treatment was addressed. She was followed up for one and a half year. ③ Case 3, a 50- year- old man, diagnosed as monoclonal gammopathy of undetermined significance and AVWS, was referred to our hospital for presentation with significant hematomas. VWF∶ Ag was reduced to 12%. VWF- containing cryoprecipitate, plasma, intravenous immunoglobulin and rituximab were used to control his bleeding symptom. During the follow-up, spontaneous hemorrhage still occurred occasionally. CONCLUSIONS: Acquired von Willebrand syndrome presented with heterogeneous symptoms. The level of VWF∶Ag and VWF∶Rco for patients with bleeding disorder should be performed. Abnormal bleeding symptoms in elderly patients without personal or family history of bleeding should prompt consideration of the underlying disorders. Treatment included controlling acute bleeding, curing the underlying diseases and preventing bleeding in high- risk situations. The prognosis of acquired von Willebrand syndrome is mainly related to the underlying diseases.

Knockdown of eIF3a attenuates the pro-fibrogenic response of hepatic stellate cells induced by TGF-ß1.

Activation of hepatic stellate cells (HSCs) plays an important role in the development of liver fibrosis. The eukaryotic translation initiation factor (eIF) 3a is the largest subunit of the eIF3 complex and has been involved in pulmonary fibrosis. However, the role of eIF3a in liver fibrosis remains largely unknown. Therefore, in this study, we investigated the role of eIF3a in transforming growth factor-ß1 (TGF-ß1)-induced HSC activation. Our results demonstrated that the expression of eIF3a was up-regulated in human liver fibrotic tissues and activated HSCs. In addition, knockdown of eIF3a suppressed TGF-ß-induced HSC proliferation and the expression of α-smooth muscle actin (α-SMA) and collagen I. Furthermore, knockdown of eIF3a inhibited the expression of p-Smad3 induced by TGF-ß1 in HSCs. These results suggest that eIF3a may function as a novel regulator to modulate HSC activation, potentially through inhibiting the TGF-ß1/Smad3 signaling pathway.

Characterization of the Microbial Communities in the Ant Lion Euroleon coreanus (Okamoto) (Neuroptera: Myrmeleontidae).

Euroleon coreanus (Okamoto) is widely distributed in China, and the larval stage can be treated as traditional Chinese medicine. However, the host-bacterium relationship remains unexplored, as there is a lack of knowledge on the microbial community of ant lions. Hence, in the current study, we explored the microbial community of the larval ant lion E. coreanus using Illumina MiSeq sequencing. Results indicated that a total of 10 phyla, 126 genera, and 145 species were characterized from the second instars of E. coreanus, and most of the microbes were classified in the phylum Proteobacteria. Cronobacter muytjensii was the most abundant species characterized in the whole body and gut of E. coreanus, and the unclassified species in the genera Brevundimonas and Lactobacillus were relatively more abundant in the head and carcass. In addition, no Wolbachia-like bacteria were detected, whereas bacteria like Francisella tularensis subsp. Holarctica OSU18 and unclassified Rickettsiella were first identified in ant lion E. coreanus.

EVALUATION OF ANTIVIRAL THERAPY TREATMENT FOR LIVER CIRRHOSIS CAUSED BY CHRONIC HEPATITIS C AND HEPATITIS C BY 31P-MRS, BASED ON METABOLITE DETECTION.

This study discusses the application of magnetic resonance spectrum (MRS) to evaluate the efficacy of antiviral therapy in the treatment of liver cirrhosis caused by chronic hepatitis C and hepatitis C, based on metabolite detection. A total of 54 patients with liver cirrhosis caused by chronic hepatitis C and hepatitis C were selected and divided into treatment group and control group. 31P-MRS imaging was carried out on patients in the two groups both before receiving antiviral treatment and 6 months after treatment to compare the change of metabolite ratio (PE+PC)/(GPE+GPC). It was revealed that no statistically significant difference was found in the comparison of (PC+PE)/(GPC+GPE) ratio in the two groups before treatment, but the difference was found 6 months after treatment; ratio of (PC+PE)/ (GPC+GPE) in the treatment group distinctly decreased 6 months after treatment compared to before treatment, with a statistically significant difference, while the control group had no remarkable change or statistical significance. Moreover, 32 patients were found with sustained virus response to antiviral therapy. Of these, 25 patients possessed a decreased ratio of (PC+PE)/ (GPC+GPE), 4 remained without change and 3 had a slightly increased ratio after antiviral treatment. Of 12 patients with no response, 1 had a decreased ratio of (PC+PE)/ (GPC+GPE), 2 remained without change and 9 had a slightly increased ratio. The differences were all statistically significant in comparison of the two groups. 31P-MRS is thought to be effective for evaluating the efficacy of antiviral therapy through non-invasive detection of liver energy metabolism.

RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

Morphological characteristics and developmental changes of the ovary in the tick Haemaphysalis longicornis Neumann.

Haemaphysalis longicornis (Ixodida: Ixodidae) is an important vector of transovarially transmitted parasites of the genus Babesia (Piroplasmida: Babesiidae). In the present study, we investigated the morphological characteristics and developmental changes of the ovary of H. longicornis. We show that the ovary of H. longicornis has a single tubular structure and is surrounded by a tunica propria. There is a longitudinal groove along one side of the ovary. During feeding and after engorgement, great changes can be observed in the ovary of H. longicornis and two rapid growth phases can be detected. The number of major protein bands of the ovary is significantly increased from day 3 of feeding and reaches a maximum on the day of engorgement. Therefore, the great diversity of proteins in the ovaries of H. longicornis can facilitate the identification of new targets for vaccine development.

RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells.

Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

Vector-mediated expression of interferon gamma inhibits replication of hepatitis B virus in vitro.

Despite the existence of efficient vaccines against hepatitis B virus (HBV) infections, these still represent a serious threat to human health worldwide. Acute HBV infections often become chronic, marked by liver cirrhosis and hepatocellular carcinoma. Promising results with interferons alpha or gamma (IFN-α, γ) or nucleoside/nucleotide analogs in inhibiting HBV replication in vitro have led to therapeutic applications to chronic HBV patients, however, their results so far have not been satisfactory. The treatments were either not effective in all patients or had adverse effects. Certain progress was expected from expression of interferons targeted to liver by adenovirus vectors, however, this approach turned out to be limited by undesired expression of toxic viral genes and high production costs. Therefore, in this study, we attempted to inhibit HBV replication in HepG2.2.15 cells by human IFN-γ expressed through a non-viral vector, an eukaryotic plasmid. The results demonstrated that IFN-γ, targeted to HBV-replicating cells, significantly inhibited the virus growth without inducing apoptosis and indicated that local expression of this kind of cytokine may be a promising strategy of gene therapy.