[A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA].

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Long-term survival case of a non-small cell lung cancer bone metastasis patient treated with bone cement, radiation and gefitinib.

OBJECTIVE: We explore the treatment of bone metastases in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We reported a 76-year-old female patient, who was diagnosed with NSCLC with bone metastasis eight years ago (stage IVA). Due to unbearable diarrhea, she refused chemotherapy, and we adopted local treatment, including local radiotherapy 50 Gy and bone cement to lumbar spinal metastases, 62 Gy local radiotherapy of primary lung tumor, TKI inhibitor gefitinib and zoledronic acid. RESULTS: She survived more than eight years and is still in follow-up. CONCLUSIONS: The median survival time for NSCLC patients with bone metastases is often less than 1 year. We reported the patient with more than eight years of survival, showed that some special cases can adopt the methods of local treatment including bone cement, treatment benefit patients, radiation therapy and targeted therapy in clinic to expand the survival.

Progress in the study of markers related to glioma prognosis.

OBJECTIVE: In the era of precision medicine, molecular and genetic biomarkers act as the key indicators for glioma patients' recurrence and prognosis. MATERIALS AND METHODS: We summarize the biomarkers of glioma prognosis from molecular level, gene level and microRNA level. RESULTS: In molecular biomarkers, cyclinD1 high expression/P16 low expression, MIF high expression and VEGF high expression were all related to glioma patients' poor prognosis; in genetic biomarkers, MGMT promoter methylation absence, IDH1 wild type, HIF-α high expression, Chromosome 1p/19q non-deletion and TERT promoter mutation were associated with poor prognosis for glioma; in microRNA biomarkers, miR-524-5p, miR-586, miR-433, miR-619, miR-548d-5p, miR-525-5p, miR-301a, miR-210, miR-10b-5p, miR-15b-5p and miRNA-182 high expression, miR-124, miR-128, miR-146b and miR-218 low expression were commonly seen in glioma poor prognosis patients. CONCLUSIONS: With the continuous development of science and technology, the diagnosis of glioma will tend to the gene and molecular level. Finding specific markers is helpful for the early diagnosis and accurate prognosis of glioma, which provides the possibility for individualized treatment.

Comparison of IMRT and VMAT radiotherapy planning for Graves' ophthalmopathy based on dosimetric parameters analysis.

OBJECTIVE: To compare volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) for the treatment of Graves' ophthalmopathy (GO) based on the dosimetric data. PATIENTS AND METHODS: 19 patients diagnosed with GO were recruited in this study. For each patient, a dual-partial-arc VMAT plans and a 7-fixed-field IMRT plans were replanned. Dosimetric parameters of the targets and organs at risk (OARs) originated from the two kinds of plans were compared and analyzed. RESULTS: Homogeneity index (HI) was superior in IMRT plans compared with VMAT (p=0.0014) but there was no significant statistical difference in conformity index (CI) between them (p=0.0673). IMRT plans revealed advantage in the OARs protection especially for the left and right lenses, optic nerves and eyeballs (p<0.05). CONCLUSIONS: VMAT and IMRT are both feasible techniques in radiotherapy in GO from the perspective of dosimetric parameters. Homogeneity and OAR protection were slightly superior in IMRT plans compared with VMAT plans.

H3K27M mutant diffuse midline glioma: a case report.

OBJECTIVE: Diffuse midline glioma with H3K27M mutation is a new tumor type of WHO central nervous system tumor classification. It often occurs in the midline structure and usually has a poor prognosis. CASE REPORT: A 38-year-old male patient presented with 2 years history of right limb with facial numbness, tumors in the left thalamic region and lateral ventricle was detected by imaging. The patient underwent the first surgery. RESULTS: The pathological examination results: Glioblastoma. He recovered well after surgery and received a total of 30 times of radiotherapy and temozolomide for one year. Fourteen months later, tumours were observed in the left thalamic region and left parieto-occipital lobe, the patient underwent the second operation. Immunohistochemistry showed: H3K27M(+). He experienced limitation of right limb movement after surgery and started taking oral apatinib 250 mg qd. After one-year, multiple tumors were found in the left brainstem, bilateral ventricles, bilateral basal ganglia, etc. The patient was given radiotherapy 7 times and then took apatinib 250 mg qd. Now the patient is still alive. CONCLUSIONS: H3K27M mutant diffuse midline glioma is characterized by diffuse infiltrative growth. Its pathological classification is diverse, imaging features lack specificity, and prognostic factors are complex. Traditional radiochemotherapy has limited effects, molecular targeted therapy, especially intervention of epigenetic regulation is being explored.

[Advances in the study of cirrhosis and precancerous lesions of liver cancer].

Liver cirrhosis is a common kind of chronic liver diseases, with the development of diseases; some patients may gradually develop precancerous lesions, or even progress to hepatocellular carcinoma (HCC). Precancerous lesions of the liver mainly include dysplastic foci (DF) and dysplastic nodules (DN), and most of it occurs on the basis of liver cirrhosis. Thus, recognition of precancerous lesions and liver cirrhosis through screening, combined with imaging and pathological features will identity the nature of nodules in early stage cirrhosis and HCC, and thereby will help to improve the diagnosis rate and clinical prognosis.

Cost-utility analysis of antiviral use under pandemic influenza using a novel approach - linking pharmacology, epidemiology and heath economics.

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

[Retrospectively analysis on 95 postpartum hemorrhage women treated with obstetrics and gynecology in intensive care unit].

Objective: To review the clinical aspects and pathogenesis of postpartum hemorrhage (PPH) and investigate the optimal protocols for intervention. Methods: From February 2009 to December 2015, data of normal labour and casearean birth women admitted to intensive care unit (ICU) in our hospital because of hematobilia were selected. 95 patients were divided into three groups (e. g ≥500-1 000 ml, ≥1 000-1 500 ml, ≥1 500-2 500 ml and ≥2 500 ml group) according to the bleeding volume. A retrospective analysis was performed to study the pathogenesis of PPH, organ function, surgical intervention and clinical prognosis on hemorrhage. Results: The data comprised 20 504 women over the 6-year period. 95 (0.463%) of which resulted in PPH and were admitted to ICU. 9 of these patients with PPH unsurvived. The value of creatinine and urea nitrogen, the score of APACHE Ⅱ and the possibility of multiple organ dysfunction syndromethe (MODS) increased with the amount of bleeding (P<0.05). For patients with PPH caused by injury of birth canal and/or placenta factors, there was significant difference among three groups on amount of bleeding (P<0.05). For patients with surgical intervention such as vaginal packing, interventional treatment and exploratory laparotomy conducted in 6 hours, the volume of transfusion was(759±114) ml. The volume of transfusion was (2 000±829) ml and (4 999±1 699) ml in 6 to 12 hours intervention group and in greater than 12 hours intervention group, respectively. The volume of transfusion significant increased over intervention time. There was a statistically significant difference in all groups (P<0.05). Conclusions: Classified treatment should be conducted according the classification on the amount of bleeding. Patients with severe PPH and/or tendency of organ failure should be admitted to ICU. Measures for maintenance of the function of organs are necessary, while appropriate surgical intervention is also needed based on the cooperation between ICU and obstetrical department, and the cure rate could be improved.

Is universal HLA-B*15:02 screening a cost-effective option in an ethnically diverse population? A case study of Malaysia.

BACKGROUND: A strong association has been documented between HLA-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Human leucocyte antigen testing is potentially valuable in many countries to facilitate early recognition of patient susceptibility to SCARs. OBJECTIVES: To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in an ethnically diverse Malaysian population. METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed epilepsy among adults: (i) carbamazepine initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to carbamazepine initiation; and (iii) alternative treatment [sodium valproate (VPA)] prescribing without HLA-B*15:02 screening. Base-case analysis and sensitivity analyses were performed over a lifetime time horizon. Incremental cost-effectiveness ratios were calculated. RESULTS: Both universal HLA-B*15:02 screening and VPA prescribing were dominated by current practice. Compared with current practice, universal HLA-B*15:02 screening resulted in a loss of 0·0255 quality-adjusted life years (QALYs) at an additional cost of 707 U.S. dollars (USD); VPA prescribing resulted in a loss of 0·2622 QALYs at an additional cost of USD 4127, owing to estimated differences in antiepileptic treatment efficacy. CONCLUSIONS: Universal HLA-B*15:02 screening is unlikely to be a cost-effective intervention in Malaysia. However, with the emergence of an ethnically diverse population in many other countries, this may render HLA-B*15:02 screening a viable intervention when an increasing proportion of the population is at risk and an equally effective yet safer antiepileptic drug is available.

CLC-3 Cl- channel-mediated invasion and migration of human ovarian cancer cells.

OBJECTIVES: To investigate the potential role of CLC-3, a member of the voltage-gated chloride channel (CLC) superfamily, in invasion and migration of ovarian cancer cell line SKOV3. MATERIALS AND METHODS: CLC-3 antisense oligonucleotides were transfected into ovarian cancer cell line SKOV3, and its effects on cell invasion and migration were analyzed by using Transwell chamber assay and wound healing assay in vitro. The efficiency of CLC-3 antisense was determined with RT-PCR and Western blotting. The protein concentrations of matrix metalloproteinase (MMP)-2, MMP-9, and vascular endothelial growth factor (VEGF) were determined using ELISA kits. Cell volume measurements were performed. RESULTS: Studies in vitro revealed that the CLC-3 antisense inhibited invasion and migration of ovarian cancer cell line SKOV3. CLC-3 antisense treatment decreased protein levels of MMP-2, MMP-9, and VEGF in culture medium of SKOV3 cells. In addition, the authors found that the capability for regulatory volume decrease (RVD) was much attenuated in SKOV3 cells transfected with CLC-3 antisense. CONCLUSIONS: These results strongly suggest that CLC-3 may get involved in proliferation, invasion, and migration of ovarian cancer cells and thus may be a useful therapeutic target.

Intrahepatic IFN-alpha expression in liver specimens from HBV-infected patients with different outcomes.

BACKGROUND: Interferon-alpha (IFN-α), an active cytokine, plays an important role in antiviral host responses, including protection against hepatitis B virus (HBV) infection. This study was designed to investigate the correlation between intrahepatic IFN-α expression levels and disease severity using liver biopsy specimens from HBV-infected patients with different outcomes. PATIENTS AND METHODS: Immunohistochemistry (IHC) was performed to detect intrahepatic IFN-α expression in liver biopsy specimens obtained from 69 HBV-infected patients with different outcomes (including 23 cases with chronic hepatitis B [CHB], 18 cases with severe hepatitis B [SHB], and 28 cases with liver cirrhosis [LC]). In situ hybridization (ISH) was carried out to measure the levels of HBV DNA in liver samples. In addition, the liver specimens of 33 healthy liver transplant donors without detectable liver diseases comprised a normal control (NC) group. RESULTS: The intrahepatic expression levels of IFN-α were higher in the HBV-infected patients than the NC group (p = 0.001). Intrahepatic IFN-α expression was also significantly higher in the SHB and CHB groups compared to the NC group (p = 0.001 and p = 0.001, respectively), while the intrahepatic HBV DNA levels of the SHB patients were higher than those of LC patients (p = 0.013). Furthermore, intrahepatic IFN-α expression was positively correlated with serum alanine aminotransferase (ALT) levels in CHB patients; no significant correlations were discovered between intrahepatic IFN-α expression and intrahepatic HBV DNA levels in all other sub-groups. CONCLUSIONS: Intrahepatic IFN-α expression may correlate with liver inflammation after hepatitis B virus infection, and IFN-α may play a vital role in the occurrence of SHB.

Effects of volume-activated chloride channels on the invasion and migration of human endometrial cancer cells.

OBJECTIVE: To investigate the role of volume-activated chloride channels (VACC) in invasion and migration of human endometrial cancer cell. MATERIALS AND METHODS: Expression of voltage-gated chloride channel-3 (CLC-3) was detected by employing reverse transcriptase-polymerase chain reaction (RT-PCR) in human endometrial cancer Ishikawa cell line. Cell invasion and cell migration were determined by using the Transwell invasion and migration assay, respectively. NPPB, a Cl- channel blocker, was treated to observe the effects of volume-activated Cl- channel on invasion and migration of endometrial cancer cell. RESULTS: CLC-3 RNA expression was observed in Ishikawa cell line. The authors showed that blockade of Cl- channels specifically inhibited invasion and migration of endometrial cancer Ishikawa cell line in a dose-dependent manner. VACC activation and subsequent regulatory volume decrease (RVD) were markedly suppressed by NPPB. Anion replacement studies indicate that permeation of Cl- ions through endometrial cancer Cl- channel is obligatory for regulatory volume decrease (RVD) induced by VACC. Moreover, [Ca2+]i measurements indicated that VACC-mediated increase in [Ca2+]i was one of the mechanisms of cancer cell invasion and migration. CONCLUSIONS: These data intensely suggest that VACC in endometrial cancer may facilitate tumor invasion and migration, presumably through inducing RVD and mediating [Ca2+]i increase.

The expression of glutathione peroxidase-1 and the anabolism of collagen regulation pathway transforming growth factor-beta1-connective tissue growth factor in women with uterine prolapse and the clinic significance.

OBJECTIVES: To investigate the expression of the anabolism of collagen regulation pathways connective tissue growth factor (CTGF) -transforming growth factor-betal (TGF-beta1) and glutathione peroxidase-1 (GPx1) in women with uterine prolapse and a study of the clinic significance. MATERIALS AND METHODS: The expression of TGF-beta1, CTGF, and GPx1 was detected by immunohistochemical staining in pubocervical fascia tissue of 30 women with uterine prolapse, including ten cases of POP-QII, ten cases of POP-QIII, ten cases of POP-QIV, and 20 cases were control group with non-prolapse and non-malignant lesions. RESULTS: There was a negative correlation between the POP-Q and expression of TGF-beta1. With the increase of POP-Q degree, the expression degree of TGF-beta1 decreased correspondingly, which also applied to CTGF and GPx1. On the other hand, there was a positive correlation between TGF-beta1 and CTGF. The synergistic change trend was found between TGF-beta1 and CTGF. It could also be seen between CTGF and GPx1 and betweenTGF-beta1 and GPx1. CONCLUSION: The expression of the antioxidase GPx1 in pelvic support structure of POP women was decreased, which resulted in the antioxidation reduced. It could break the balance of oxidation and antioxidation in pelvic support structure, and may induce an increase of ROS level and the down-regulation of TGF-beta1-CTGF pathway. It could inhibit the anabolism of collagen and injury the pelvic support structure, thus promoting the occurrence and development of POP.

Carrier screening and prenatal diagnosis for alpha-thalassemia with biphasic polymerase chain reaction.

Alpha-thalassemia is the most common single gene disorder in Taiwan and Southeast China. The majority of alpha-thalassemic mutations in this area are alpha-thalassemia 1. Homozygous alpha-thalassemia 1 has been recognized as the most important cause of hydrops fetalis. To investigate the incidence of alpha-thalassemia 1 mutations and to characterize its molecular defects, cord blood electrophoresis was performed on 2,000 newborns, of which 99 (5%) cases were found to have hemoglobin (Hb) Bart's levels > 3.0%. A methodology using biphasic polymerase chain reaction (PCR) with nesting primers was developed to characterize the alpha-thalassemia 1 Southeast Asia type (SEA) deletion in the cases with detectable Hb Bart's levels. The SEA deletion was found in 92 (93%) of 99 cases. Prenatal screening was performed on couples with abnormal hematologic indices, and PCR was used to detect couples heterozygous for SEA deletion. Prenatal diagnosis was performed in 21 cases, and four cases were found to have a homozygous SEA deletion. This strategy can be applied to couples who need prenatal genetic counseling for alpha-thalassemia major in this area.