[A case report of chronic granulomatous disease with CYBB gene mutation in an adult].

We reported a 28-year-old male patient who had been admitted to a local hospital for several times in the past four years because of recurrent fever and cough. Each chest CT scan during hospitalization showed consolidation accompanied by exudation and mild pleural effusion. After treatment, the consolidation apparently absorbed, but similar symptoms recurred within half a year, and the new consolidation appeared. For this reason, he was diagnosed with tuberculosis or bacterial pneumonia several times in other hospitals, and was hospitalized two to three times a year. Finally, he was diagnosed with chronic granulomatous disease (CGD) with CYBB gene mutation through whole-exome sequencing.

[Clinical significance of ultrasound combined with serological indexes for predicting nonalcoholic fatty liver disease in patients with chronic hepatitis B with normal or slightly elevated alanine aminotransferase].

Objective: To investigate and establish the related factors of non-invasive score model for prediction of non-alcoholic fatty liver disease in chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase (ALT). Methods: A total of 128 cases with chronic hepatitis B who had undergone liver biopsy were included. According to the presence or absence of hepatocyte steatosis on the pathological results of liver biopsy, they were divided into a fatty infiltration and a non-fatty infiltration group. Patients' demographic characteristics, laboratory test indexes, and pathological test results were collected. Univariate and multivariate logistic regression analysis combined with clinical screening variables were used to establish a predictive model. The prediction efficiency of the new model was evaluated by the receiver operating curve, and the difference between the accuracy of the new model and ultrasound in the diagnosis of fatty liver was compared by Delong's-test. Result: Multivariate regression analysis showed that serum triglyceride, serum uric acid and platelets were highly correlated with intrahepatic steatosis (P<0.05). The regression equation triglyceride-uric acid-platelet (TUP)-1=-8.195+0.011×uric acid+1.439×triglyceride+0.012×platelet count was established by combining the above variables. Tthe equation TUP-2=-7.527+0.010×uric acid+1.309×triglyceride+0.012×platelet count+1.397×fatty liver (ultrasound) was established (yes=1; no=0) after incorporating the results of abdominal ultrasound. The diagnostic value of TUP-1 and TUP-2 models for fatty liver was better than that of ultrasound alone and there was no statistically significant difference in diagnostic value between TUP-1 and TUP-2 models (Z=1.453, P=0.146). Conclusion: Compared with abdominal ultrasonography alone, the new model is more effective in diagnosing fatty liver and has good application value.

[Risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis treated with long-term nucleos(t)ide analogues].

Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

[Liver histological status and clinic outcome in HBeAg-negative chronic hepatitis B with low viral load].

Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs. 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

Retraction Note: Long non-coding RNA FAL1 regulated cell proliferation through Akt pathway via targeting PDK1 in esophageal cancer cells.

The article "Long non-coding RNA FAL1 regulated cell proliferation through Akt pathway via targeting PDK1 in esophageal cancer cells", by X.-S. Liang, Y. Sun, T. Liu, published in Eur Rev Med Pharmacol Sci 2018; 22 (16): 5214-5222-DOI: 10.26355/eurrev_201808_15719-PMID: 30178844 has been retracted by the authors for the following reasons. The authors asked to retract this manuscript as they identified some problems with the data reported, and the dilution ratio of the antibody during the Western blot experimental operation is incorrect. In this article, the dilution of antibodies is described as follows: anti-cyclin D 1 (dilution 1:500, Abcam, Cambridge, MA, USA), anti-MMP7 (dilution 1:500, Santa Cruz Biotechnology, Santa Cruz, CA, USA), anti-p21 (dilution 1:400, Cell Signaling Technology, Danvers, MA, USA), anti-p-Akt (dilution 1:500, Abcam, Cambridge, MA, USA), anti-Akt (dilution 1:500, Abcam, Cambridge, MA, USA), and anti-p-actin (dilution 1:500, Santa Cruz Biotechnology, Santa Cruz, CA, USA). Nonetheless, authors affirm they only used a dilution of 1:200 for all antibodies, undermining the Western blot experimental operation. Thus, the article's conclusions are considered invalid and unreliable. This article has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/15719.

Risk factors for acute hepatitis B and its progression to chronic hepatitis in Shanghai, China.

BACKGROUND AND AIMS: The major risk factors for acute hepatitis B (AHB) in China and the viral factors determining the progression from acute to chronic hepatitis B remain largely unknown. METHODS: Epidemiological studies within a population-based surveillance for AHB in adults were performed in Shanghai, China, including 294 patients, 588 matched controls and 572 family members of the patients. RESULTS: Invasive medical procedures, household contact with hepatitis B virus (HBV) carriers, body care and beauty treatments, and lack of HBV vaccination were independently associated with AHB. Among those risks, pedicure in bath centres emerged. Sixty-eight of 128 patients with AHB were genotyped including 33 with HBV B2 and 35 with HBV C2. Twenty-five (8.50%) of the 294 patients, including 20 with HBV C2 and 5 with HBV B2 (p = 0.013), progressed to chronic infection. Multivariate analysis showed that HBV C2 was independently associated with chronicification of AHB. Patients with HBV B2 were younger and there was a higher proportion of women than those with HBV C2. The prevalence of HBV B2 was higher in the patients than in neighbourhood chronic carriers. The chronic carriers with HBV B2 showed higher viral loads, higher hepatitis B e antigen (HBeAg) seropositivity, and with higher proportion in men than those with HBV C2, implying that sexual contact plays a role in the transmission of HBV B2. Phylogenetic analysis showed that HBV C2 was frequently involved in transmissions within households. CONCLUSIONS: Despite lower viral load and HBeAg status in the chronic carriers, HBV C2 was more prone to causing chronic infection than was HBV B2.

Long non-coding RNA FAL1 regulated cell proliferation through Akt pathway via targeting PDK1 in esophageal cancer cells.

OBJECTIVE: Esophageal cancer (EC) is one of the most common cancers in the world. Long non-coding RNA focally amplified lncRNA on chromosome 1 (FAL1) is an oncogene which is frequently and focally amplified in human cancers. However, the role of FAL1 in EC remains unknown. The aim of the present study was to evaluate the effect of FAL1 on EC cell lines and explore the underlying mechanism. PATIENTS AND METHODS: The expression levels of FAL1 in EC tissues and cell lines were detected by RT-PCR. Then, Eca109 cell, a human esophageal cancer cell line, was transfected with FAL1-overexpressing vector or FAL1-siRNA or empty vector. The cell proliferation was measured by MTT assay. The cell apoptosis was assessed by TUNEL assay. The cell invasion was determined by transwell assay. The interaction effect between FAL1 and 3-phosphoinositide-dependent protein kinase 1 (PDK1) was evaluated by chromatin immunoprecipitation (ChIP) assay. RESULTS: FAL1 was significantly up-regulated in EC tissues and human EC cell lines including Eca109, KYSE150, Eca9706, Kyse30, and TE-1 cells. Overexpression of FAL1 promoted cell proliferation, invasion ability, and cell cycle, but it inhibited cell apoptosis in EC cell lines. Overexpressed FAL1 activated Akt pathway via interacting with PDK1 in EC cell lines. CONCLUSIONS: FAL1 regulated cell proliferation through Akt pathway via targeting PDK1 in EC cells. These findings revealed that FAL1 exhibited oncogenic activity in EC, and inhibiting FAL1 might be useful for preventing the progression of EC.

[Tumor necrosis factor in peritoneal fluid of infertile women with endometriosis and its relation to sperm motility].

Tumor necrosis factor (TNF) of 16 infertile women with endometriosis was measured in their peritoneal fluid (PF) with double monoclonal antibody ELISA method, and its effect on sperm motility and membrane integrity was evaluated by semen analysis and hypoosmotic swelling test (HOS). Comparing with that of infertile women without endometriosis (n = 11) and normal fertile women (n = 7), the level of PF-TNF was significantly higher in women with endometriosis (P < 0.01), in accord with the stage of the disease. In the PF of these patients after incubation with the donor sperms, the percentages of forward movement, total motility and hypoosmotic swelling of the donor sperms were significantly decreased (P < 0.01), showing a negative correlation to TNF levels. These results indicate that the elevation of PF-TNF in endometriosis has detrimental effect on sperm function.

Developing gossypol derivatives with enhanced antitumor activity.

Preclinical and clinical studies have pointed to the antitumor potential of the naturally occurring polyphenolic binaphthyl dialdehyde, gossypol, as well as its purified (-,+) enantiomers. To explore further the antitumor properties of this multifunctional agent, we synthesized several reactive derivatives including the (-,+) enantiomers of gossypolone and four different gossypol Schiff's bases (AR1, AR2, AR3, AR4). The biological activities of these new agents were screened by measuring their in vitro antiproliferative activity against malignant (MCF-7, MCF-7/adr) or immortalized (HBL-100) human breast epithelial cell lines. Racemic gossypolone showed relatively uniform antiproliferative activity against all of the breast epithelial cell lines with 3- to 5-fold less activity than (--)-gossypol against MCF-7 and MCF-7/adr cells. Of interest, the relative antitumor potency of purified gossypolone enantiomers was reverse that of gossypol enantiomers, since (+)-gossypolone showed up to 3-fold greater inhibition of MCF-7 culture growth than (--)-gossypolone. Of the Schiff's base derivatives only AR3 with its isopropyl amine substituent demonstrated cytotoxic activity comparable to that of (--)-gossypol; derivatives with ethyl, propyl, or butyl amine substituents (AR1, AR2, AR4) had little growth inhibitory activity at culture concentrations up to 25 microM. AR3 activity was greatest against HBL-100 and MCF-7 cells [MCF-7 IC50 values: AR3 = 0.9 microM, (--)-gossypol = 2.3 microM]; unlike (--)-gossypol, however, AR3 showed substantially reduced activity against the multidrug-resistant subline, MCF-7/adr. These structure-activity comparisons suggest that isolation of (-,+)-enantiomers of AR3 and additional chemical modifications including the synthesis of an isopropyl amine Schiff's base of gossypolone will likely yield a newer generation of gossypol analogues with enhanced anticancer potential.