[Real-world study on the efficacy and safety of first-line antiviral therapy for chronic hepatitis B].

Objective: To clarify the clinical efficacy of first-line oral antiviral drugs tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), and entecavir (ETV) in the treatment of chronic hepatitis B (CHB) and their safety profiles with lipid, bone, and kidney metabolism. Methods: 458 CHB cases diagnosed and treated at the Department of Hepatology of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University from February 2010 to November 2022 were selected. TAF (175 cases), TDF (124 cases), and ETV (159 cases) were used as therapies. At 24 and 48 weeks, the virology, biochemical response, changes in liver stiffness measurement (LSM), and bone, kidney, and blood lipid metabolism safety profiles were compared and analyzed. Results: After 24 and 48 weeks of TAF, TDF, and ETV therapy, HBV DNA load decreased by 3.28, 2.69, and 3.14 log10 IU/ml and 3.28, 2.83, and 3.65 log10 IU/ml, respectively, compared with the baseline, and the differences between the three groups were statistically significant, P < 0.001. The complete virological response rates were 73.95%, 66.09%, 67.19%, and 82.22%, 72.48%, and 70.49%, respectively. The incidence rates of low-level viremia were 16.67%, 21.70%, and 23.08%, while poor response rates were 1.11%, 3.67%, and 4.10%. ALT normalization rates were 64.00%, 63.89%, 67.96%, and 85.33%, 80.56%, 78.64%, respectively, and there was no statistically significant difference among the groups. LSM was significantly improved in patients treated with TAF for 48 weeks, P = 0.022. Serum phosphorus level gradually decreased with the prolongation of TDF treatment. The TAF treatment group had a good safety profile for kidney, bone, and phosphorus metabolism, with no dyslipidemia or related occurrences of risk. Conclusion: There are some differences in the therapeutic effects of first-line anti-HBV drugs. TAF has the lowest incidence of low-level viremia after 48 weeks of treatment and has a good safety profile in kidney, bone, and blood lipid metabolism.

[Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma].

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

[Precise immunological classification guidance for early initiation of antiviral therapy in patients with chronic HBV infection].

Chronic hepatitis B virus (HBV) infection is a major problem affecting global public health. Appropriate antiviral therapy use can prevent or delay the occurrence of liver cirrhosis and liver cancer. Precise immunological classification can be helpful to formulate personalized therapy and management plans for HBV-infected patients. Antiviral therapy should be started early in those who meet antiviral indications, and nucleos(t)ide analogue therapeutic regimens alone or in combination with pegylated interferon alpha should be optimized according to antiviral therapy response, in order to maximize the realization of virological and serological response, improve clinical cure rate, and enhance long-term prognosis.

[CK7+/CD117- low grade oncocytic tumor of the kidney: a clinicopathological analysis].

Objective: To investigate the clinicopathological, immunohistochemical and molecular characteristics of low grade oncocytic tumors (LOT) of the kidney with CK7+/CD117- staining pattern for enhancing the understanding of renal LOT. Methods: The clinical data, histological morphology and immunophenotypes of seven renal LOT cases diagnosed at the Department of Pathology, the First Affiliated Hospital, Zhejiang University School of Medicine from January 2017 to April 2021 were analyzed. The patients were followed up. Among the seven patients, five underwent high-throughput DNA targeted sequencing, and their molecular characteristics were analyzed. Results: The patients' age ranged 59-82 years, with an average of 70 years. There were 2 males and 5 females. The boundary of the tumor was clear. The tumor cells had homogeneous eosinophilic cytoplasm and round or oval nuclei, with a perinuclear halo. Small basophilic nucleoli were conspicuous (WHO/International Society of Urological Pathology grade 2). In the hypercellular areas, the tumor cells were mainly arranged in dense solid or nest. In the stroma, there were dilated veins, thick-walled arterioles and thick collagen fiber bundles that divided the cells into pseudonodules. In the sparsely cellular area, the tumor cells were arranged in the so-called "tissue culture" fashion. In addition, the stroma contained fresh hemorrhagic foci and lymphoid aggregates. High-throughput sequencing of 5 cases revealed that one case harbored mTOR gene missense mutation and another case harbored TSC1 frameshift mutation. Conclusions: LOT of the kidney is an indolent tumor with an overall good prognosis. Pathologists should not misdiagnose it as renal oncocytoma and chromophobe renal cell carcinoma.

Pharmacokinetic Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Distinguishing Hepatocellular Carcinoma From Cholangiocarcinoma in Pre-Liver Transplantation Evaluation.

OBJECTIVE: Liver transplantation for intrahepatic cholangiocarcinoma is notorious for rapid recurrence with poor survival rate postoperatively and has therefore been discontinued in most centers. The purpose of this study is to distinguish hepatocellular carcinoma (HCC) from cholangiocarcinoma in pretransplantation imaging evaluation by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: From January 2014 to September 2015, 19 patients were included in the study, with a mean age of 62.8 years. All subjects underwent pretransplantation DCE-MRI and surgical excision or core biopsy. The DCE-MRI parameters were measured using the Tofts model 1999. Statistical analysis included nonparametric tests and area under the curve for the receiver operating characteristic. RESULTS: Fourteen HCCs and 5 cholangiocarcinomas were diagnosed by surgical pathology. The mean size of tumor was 6.4 cm (range, 1.5 cm to 13.7 cm). All DCE-MRI parameters were calculated as the ratio between the tumor and normal liver parenchyma and K(trans) (1/min) was used as a distinguishing parameter between the two tumors. K(trans) was higher in the cholangiocarcinoma group (1.89 ± 1.13) than in the HCC group (0.46 ± 0.35). Univariate analysis revealed that K(trans) has a high significant difference (P = .001). The optimal K(trans) value cutoffs were 1 or more (area under the curve = 0.971) for detection of HCCs or cholangiocarcinomas. CONCLUSION: The analysis of DCE-MRI with the kinetic model (Tofts, 1999) presents a new and practical approach indiscrimination of HCC from cholangiocarcinoma for pretransplantation imaging evaluation.

Portal venous pressure in adult living donor liver transplantation.

OBJECTIVE: The relationship between portal pressure and small-for-size syndrome (SFSS) is unsettled. The purpose of this study was to evaluate the role of portal pressure in predicting SFSS. METHODS: Thirty-four patients with end-stage liver disease who received adult-to-adult living-donor liver transplantation (ALDLT) were included. Recipients were grouped based on whether they received portal flow modulation or not. The intraoperative portal vein flow volume (PVFV) and portal venous pressure (PVP) between the 2 groups were compared. The relationship of PVP to PVFV, graft weight-to-recipient weight ratio (GRWR), and graft weight-to-recipient spleen size ratio (GRSSR) were analyzed. RESULTS: Persistent portal hypertension was found after ALDLT. The PVP was linearly correlated with PVFV but not with GRWR or GRSSR. With the use of the following criteria, (1) PVFV >250 mL/min/100 g graft weight, (2) GRWR <0.8%, and (3) GRSSR <0.6, modulation of the portal flow was performed in 3 cases. The receiver operating characteristic analysis showed that 23 mm Hg was the cutoff point for PVP, with a sensitivity of 83% and specificity of 43%. CONCLUSIONS: PVP is a weak parameter to use for portal flow modulation after ALDLT. It is sensitive but not specific to predict SFSS.

In situ hybridization and RT-PCR detection of Macrobrachium rosenbergii nodavirus in giant freshwater prawn, Macrobrachium rosenbergii (de Man), in Taiwan.

Between January and March 2006, suspected outbreaks of white tail disease were observed in post-larvae and juveniles of Macrobrachium rosenbergii in hatcheries and nursery ponds at Kaohsiung and Pingtung Counties in southern Taiwan. Pathognomonic lesions showed the presence of large oval and/or irregular basophilic, cytoplasmic inclusion bodies in the infected muscles and hepatopancreas. Reverse transcriptase polymerase chain reaction (RT-PCR) assay and in situ hybridization (ISH) revealed evidence of M. rosenbergii nodavirus (MrNV) infection but did not detect extra small virus. Phylogenetic analysis indicated that there were very high identities between nucleotide sequences among six strains obtained in this study (99.5-100%), moderate identities with Caribbean and Indian strains (98.2-98.6%), but slightly lower identity with a Chinese strain (95.2%). This is the first confirmation of MrNV in giant freshwater prawns, using an RT-PCR and ISH, in Taiwan.

2-Octyl cyanoacrylate medical adhesive in treatment of a corneal perforation.

PURPOSE: To describe a case of successful treatment of a corneal perforation with 2-octyl cyanoacrylate. METHODS: 2-Octyl cyanoacrylate was applied at the slit lamp with topical proparacaine anesthesia to a cornea with an inferior perforation with iris plugging the defect. RESULTS: After application of 2-octyl cyanoacrylate, the anterior chamber was noted to deepen, and visual acuity improved to 20/200. The glue remained intact for more than 6 weeks and eventually fell out. The underlying cornea healed without scarring, vascularization, or thinning. CONCLUSION: We have described a case in which 2-octyl cyanoacrylate was used to treat a corneal perforation with excellent results. Further study of this adhesive will be useful in comparing the effectiveness and safety of 2-octyl cyanoacrylate with that of previously studied adhesives.

Retinoic acid-mediated G1 arrest is associated with induction of p27(Kip1) and inhibition of cyclin-dependent kinase 3 in human lung squamous carcinoma CH27 cells.

Retinoids are promising agents for the prevention and treatment of several human malignancies including lung cancer. In this study, the effect of retinoic acid (RA) on cell growth and the mechanism of growth modulation were examined in human lung squamous carcinoma CH27 cells. Here we report that RA mediated the dose- and time-dependent growth arrest in G1 phase, accompanied by the up-regulation of p27(Kip1) and the down-regulation of the cyclin-dependent kinase 3 (Cdk3) and p21(CIP1/Waf1) proteins. Furthermore, RA-induced growth arrest of CH27 cells was also associated with increased retinoic acid receptor beta (RARbeta) and reduced c-Myc expression. However, RA had no effect on the levels of cyclins A, D1, D3, E, or H, or on Cdk2, Cdk4, Cdk5, CDk6, Cdk7, p16(Ink4A), p15(Ink4B), p53, or pRb proteins in CH27 cells. Evaluation of the kinase activity of cyclin-Cdk complexes showed that RA increases p27(Kip1) expression in CH27 cells leading to markedly reduced cyclin A/Cdk2 kinase activity and slightly reduced cyclin E/Cdk2 kinase activity, with no effect on cyclin D/Cdk4 and cyclin D/Cdk6 activities. Moreover, coincident with the decrease in kinase activity was a drastic increase in cyclin A-bound p27(Kip1). These results suggest that increases in the levels of p27(Kip1) and its binding to cyclin A, as well as reduction of Cdk3 protein expression, are strong candidates for the cell cycle regulator that prevents the entry into the S phase in RA-treated CH27 cells, with prolongation of G1 phase and inhibition of DNA synthesis.

Cationic lipid structure and formulation considerations for optimal gene transfection of the lung.

Enhanced gene transduction to the lung using cationic lipids could be attained through optimization of the structure of the lipids and the formulation of the cationic lipid:plasmid DNA (pDNA) complexes. We have expanded on our earlier observation of the importance of the structural orientation of the cationic lipid headgroup. Through the synthesis of a number of matched pairs of cationic lipids differing only in the configuration of their headgroup, we confirmed that those harboring a T-shape headgroup are more active than their linear counterparts, at least when tested in the lungs of BALB/c mice. Additionally, we demonstrated that not only are the structural considerations of these cationic lipids important, but also their protonation state, the free base being invariably more active than its salt counterpart. The salt forms of cationic lipids bound pDNA with greater avidity, which may have affected their subsequent intracellular dissolution and transit of the pDNA to the nucleus. Inclusion of a number of frequently used solutes in the vehicle severely inhibited the gene transfection activity of the cationic lipids. The selection of neutral co-lipids was also an important factor for overall transfection activity of the formulation, with significant gains in transfection activity realized when diphytanoylphosphatidylethanolamine or dilinoleoylphosphatidylethanolamine were used in lieu of dioleoylphosphatidylethanolamine. Finally, we showed that a transacylation reaction could occur between the cationic lipid and neutral co-lipid which reduced the transfection activity of the complexes. It is the hope that as our understanding of the many factors that influence the activity of these cationic lipid:pDNA complexes improves, formulations with much greater potency can be realized for use in the treatment of pulmonary diseases.

Comparison of two molecular techniques for the detection of avian reoviruses in formalin-fixed, paraffin-embedded chicken tissues.

Reverse transcription (RT) in situ polymerase chain reaction (PCR) and in situ hybridization (ISH) techniques were used to detect the sigma c-encoded gene of avian reovirus (ARV) in chicken tissue sections. The advantage of using in situ methods is to make more rapid and accurate diagnosis of ARV infections. The sensitivity of these two techniques were compared. Of the two techniques, the RT in situ PCR test was found to be more sensitive than ISH and provided the rapid, sensitive, and specific detection of ARV infections.

Postmortem diagnosis of hemoglobin SC disease complicated by fat embolism.

A case is reported of a previously healthy 52-year-old African American male who presented with acute onset of abdominal pain. Progressive increase in his abdominal symptoms led to an exploratory laparotomy; however, no pathology was discovered. Postoperatively, the patient became hypoxemic which progressed to diffuse infiltrates on chest x-ray, suggestive of adult respiratory distress syndrome. He had a rapidly fatal course. Autopsy showed bone marrow infarction, fat embolism, splenomegaly, and widespread congestion with sickle erythrocytes. Hemoglobin electrophoresis done postmortem showed hemoglobin (Hb) SC disease that was undiagnosed antemortem. To the best of our knowledge, it is unusual for Hb SC to be diagnosed postmortem in adults. This case suggests that sickle cell disorders should be ruled out in patients at risk for hemoglobinopathy in the presence of signs and symptoms compatible with the disease, irrespective of age.

Fine needle aspiration diagnosis of ciliated hepatic foregut cysts: a report of three cases.

BACKGROUND: Ciliated hepatic foregut cysts, albeit rare, are important to consider in liver aspirates obtained for evaluation of possible neoplastic disease. CASES: In three cases, liver fine needle aspirates showed features consistent with ciliated hepatic foregut cysts. Two of these aspirates were obtained to evaluate possible metastatic disease prior to resection of primary tumors, one of the lung and one of the bladder. A third case had radiologic findings suggestive of a cystic neoplasm. The fine needle aspirate material from these cases revealed clusters of tall, columnar cells with basally oriented nuclei and prominent apical terminal plates with cilia. These features are consistent with ciliated hepatic foregut cysts. CONCLUSION: This entity, although originally described in the late 19th century, to our knowledge has not been reported to occur in fine needle aspirate material and should be included in the differential diagnosis of cystic lesions of the liver.

Isolation and characterization of CAJ1, a novel yeast homolog of dnaJ.

A novel member of the Escherichia coli dnaJ family, designated CAJ1, was isolated from a yeast expression library using antiserum against a yeast calmodulin-binding fraction. Although CAJ1 contains neither a Gly-rich region nor a Cys-rich repeat, as are found in other DnaJ relatives, it contains a leucine zipper-like motif.

cDNA cloning of an alternatively spliced isoform of the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase (calcineurin B alpha 2).

A cDNA encoding the regulatory subunit of Ca2+/calmodulin-dependent protein phosphatase, calcineurin B (CNB), was isolated from a rat testis cDNA library. It differs from the cDNA obtained from a rat brain cDNA library by an addition of 138 base pairs in the coding region. The codon of the clone from a testis library corresponding to the initiation codon of the clone from a brain library is not ATG but AAG, 5'-noncoding regions of these cDNAs are also different. The addition in the coding region results in the gain of 46 amino acids at the N-terminus. These findings suggest that two distinct isoforms of CNB alpha are derived from the same gene through a process involving alternative utilization of two promoters. We designate the brain type isoform as CNB alpha 1 and the longer isoform as CNB alpha 2. Northern blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis suggest that CNB alpha 2 is specifically expressed in the testis, and its expression is developmentally regulated.

Beta-cyclodextrin chiral stationary phases for liquid chromatography. Effect of the spacer arm on chiral recognition.

Cyclodextrins (CDs) can be bound on silica to prepare chiral stationary phases (CSPs) for liquid chromatography. The cyclodextrin ring is connected to a spacer previously bonded on the silica surface. Three different CD-CSPs were prepared with three different spacers. (i) A dimethylethoxysilane with a linear 6 carbon chain produced a monomeric layer. The bonded CD units can move and rotate freely. (ii) The corresponding trimethoxysilane produced a polymeric layer. The bonded CD units were not located at the same distance of the silica surface, but they could still move and rotate freely. (iii) The third spacer contained a cyclohexyl ring that may introduce some conformational rigidity in the CD connection to silica. The three CSPs prepared contained a CD surface coverage of about 0.3 micromol/m(2) which is approximately half of the maximum theoretical CD coverage. The first spacer was the most efficient to bond CDs with an average value of 1.7 spacers per CD ring, whereas 5.5 spacers per CD ring were needed with the two other spacers. The chiral recognition capabilities of the three phases were compared using 14 racemic compounds. No pronounced differences were noted, but the CSP prepared with the dimethylethoxysilane monomeric spacer seems to be the most efficient for chiral recognition.