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The clinical value of von Willebrand factor and VITRO score in evaluating disease progression in patients with HBV infection

Zhonghua Gan Zang Bing Za Zhi. 2022 Mar 20;30(3):309-315. doi: 10.3760/cma.j.cn501113-20210202-00061.

ABSTRACT

Objective: To explore the clinical value of von Willebrand Factor (vWF) and VITRO score (vWF:Ag/platelet count) in assessing disease progression in patients with HBV infection. Methods: Randomly collect relevant clinical data of 308 patients with HBV infection (including 154 cases of chronic hepatitis B, 66 cases of hepatitis B cirrhosis in compensatory period, 88 cases of hepatitis B cirrhosis in decompensated period) from December 1, 2018 to January 5, 2021 in the Second Affiliated Hospital of Chongqing Medical University. The vWF values are measured by a uniform optical method, and all data are included using a uniform standard. Analyze the difference and significance of plasma vWF level and VITRO score in chronic hepatitis B, hepatitis B cirrhosis in the compensatory phase and decompensated phase. Results: The plasma vWF level and VITRO score of the chronic hepatitis B group were (139.47±76.44) and (0.86±0.8), respectively, and the hepatitis B cirrhosis compensated group was (164.95±67.12 and 1.44±1.14), respectively. Hepatitis cirrhosis decompensated group were (317.48±103.32 and 6.81±4.98), respectively; plasma vWF level and VITRO score increased with the progression of HBV infection, and the difference was statistically significant (F=133.669,P=0.000F=137.598,P=0.000).The plasma vWF level and VITRO score in patients with hepatitis B cirrhosis were (185.65±85.07 and 2.3±2.37) in the Child-Pugh A group, (304.74±105.81 and 6.37±5.19) in the B grade group, and (369.48±73.238.28±5.38) in the C grade group; plasma vWF level and VITRO score in patients with hepatitis B cirrhosis increased with the increase of Child-Pugh grade, and the difference was statistically significant (F=60.236, P=0.000F=32.854, P=0.000). The area under the curve (AUC) of plasma vWF level and VITRO score for diagnosing the decompensated stage of hepatitis B cirrhosis were 0.897 [95% confidence interval (CI): 0.855-0.940, P<0.01], 0.949 [95% CI: 0.916-0.982, P<0.01). When the vWF level and VITRO score were taken as cut-off values of 238.5% and 1.65, respectively, the sensitivity of diagnosing the decompensated stage of hepatitis B cirrhosis was 79.5% and 94.3%, the specificity was 92.3% and 87.7%, and the positive predictive value was 80.5% and 94.3%, the negative predictive value was 91.9% and 97.5%, and the diagnostic accuracy was 88.6% and 89.3%. Among the patients with decompensated hepatitis B cirrhosis, the level of vWF in the group with gastrointestinal bleeding (367.24±68.29)% was significantly higher than that in the group without gastrointestinal bleeding (286.15±109.69)%, and the difference was statistically significant (P<0.001) The VITRO score of the group with gastrointestinal bleeding (9.12±5.4) was significantly higher than that of the group without gastrointestinal bleeding (5.36±4.13), and the difference was statistically significant (P<0.01). The vWF level in the spontaneous peritonitis group was (341.73±87.92)% higher than that in the non-spontaneous peritonitis group (296.32±111.74)%, and the difference was statistically significant (P<0.05). There was no statistical difference in VITRO score between the two groups. significance. Conclusion: Plasma vWF level and VITRO score can evaluate the progression of liver disease and the degree of decompensation of liver cirrhosis in patients with HBV infection, and have a predictive effect on various complications after decompensation of liver cirrhosis, and have certain guiding significance for early intervention measures.

PMID:35462488 | DOI:10.3760/cma.j.cn501113-20210202-00061

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Exploring the effects of entecavir treatment on the degree of liver fibrosis in patients with non-alcoholic fatty liver combined with chronic hepatitis B in Tibet region

Zhonghua Gan Zang Bing Za Zhi. 2022 Mar 20;30(3):304-308. doi: 10.3760/cma.j.cn501113-20200628-00347.

ABSTRACT

Objective: To explore the efficacy of entecavir antiviral therapy on the degree of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) combined with chronic hepatitis B (CHB) in Tibet region. Methods: HBeAg-positive CHB patients who were treated with entecavir in the outpatient and inpatient Department of Infectious Diseases of the Tibet Autonomous Region people’s Hospital between January 2018 to December 2019 were retrospectively analyzed. Among the 140 subjects with CHB, 95 cases were CHB alone, and the other 45 cases were diagnosed as CHB combined with NAFLD by ultrasound. All patients were given entecavir 0.5 mg orally once daily on an empty stomach for 48 weeks. HBeAg negative conversion rate, blood glucose, blood lipid, liver function and the degree of liver fibrosis were compared between the two groups at the 12th, 24th and 48th weeks of treatment to evaluate the virological response. SPSS 19.0 statistical software was used to process the data. Measurement data were expressed as mean ± standard deviation (x¯±s). Descriptive statistical analysis was used for t-test, and the categorical variables were expressed as percentage (%) and χ2 test. A p-value < 0.05 was considered as statistically significant. Results: After 48 weeks of treatment, the HBeAg and HBV DNA negative conversion rate were significantly better in patients with CHB alone (group B) than CHB combined with NAFLD (group A), that is to say, HBeAg negative conversion rate in group A and B patients were 28.90% and 40%, respectively, and group B was better than group A. HBV DNA negative conversion rate was significantly elevated in group B (83.2%) than group A (64.4%), with statistical significance (P<0.05), and the difference between the both groups was statistically significant. Alanine aminotransferase level was significantly decreased in patients with CHB alone than patients with CHB combined with NAFLD. Aspartate aminotransferase/platelet ratio index was significantly decreased after treatment than before treatment in both group of patients, and the depletion was more pronounced in CHB alone group. Liver stiffness values were significantly decreased in patients with CHB combined with NAFLD than CHB alone group. Moreover, liver stiffness values was higher in group A than group B before treatment under the influence of fat attenuation factors, and the differences before treatment and after treatment were 3.50±4.66 and 2.05±2.53, respectively; however, group B was not affected by fat attenuation factors, so LSM value reduction in group A was more obvious, and the differences were statistically significant. There was no statistically significant difference in blood glucose and blood lipids levels before and after treatment between the two groups. Conclusion: NAFLD has a certain effect on antiviral therapy and liver fibrosis in patients with CHB, i.e., the effect of antiviral therapy in patients with CHB alone is better than patients with CHB combined with NAFLD. Patients with CHB combined with NAFLD when treated with antiviral therapy had a significantly greater degree of liver stiffness reduction than patients with CHB alone. Therefore, it is necessary to actively intervene the risk factors associated with NAFLD according to the actual situation of different individuals to improve clinical efficacy of antiviral therapy.

PMID:35462487 | DOI:10.3760/cma.j.cn501113-20200628-00347

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Immediate postoperative color Doppler ultrasonography on the diagnosis of hemorrhagic complications of liver biopsy and its directed compression hemostasis

Zhonghua Gan Zang Bing Za Zhi. 2022 Mar 20;30(3):285-289. doi: 10.3760/cma.j.cn501113-20200809-00446.

ABSTRACT

Objective: To study the diagnostic value of immediate color Doppler ultrasonography on traumatic hepatic hemorrhage after tissue sampling with ultrasound-guided liver biopsy and the clinical effect of its-directed local compression hemostasis at puncture-site. Methods: 132 hospitalized patients with various liver diseases underwent ultrasound-guided hepatic puncture-biopsies, including 61 cases with diffuse parenchymal and 71 cases with focal liver lesions. Immediate postoperative color Doppler ultrasonography was performed following liver biopsy. Abnormal blood flow signal was observed at hepatic puncture biopsy site, and if there were hemorrhagic signals, ultrasound-directed local compression hemostasis was performed until the bleeding signal disappeared. F-test and Chi-square test were used for statistical analysis. Results: Immediate color Doppler ultrasonography showed traumatic hemorrhage in 36.1% (22/61) and 40.8% (29/71) cases of diffuse liver disease and focal liver disease group, respectively. All hemorrhagic signals were eventually disappeared after ultrasound-directed local compression hemostasis. The median hemostasis time was 2 min in both groups, and there was no statistically significant difference in bleeding rate and hemostasis time between the two groups (P>0.05). There were no serious complications and deaths. Conclusion: Traumatic hepatic hemorrhage along the needle puncture tract is a common accompanying condition during liver biopsy. Immediate postoperative color Doppler ultrasonography can trace bleeding signals in timely manner and direct effective compression hemostasis, so it should be used routinely to help avoid occurrence of severe hemorrhagic complications.

PMID:35462484 | DOI:10.3760/cma.j.cn501113-20200809-00446

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Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis

Zhonghua Gan Zang Bing Za Zhi. 2022 Mar 20;30(3):279-284. doi: 10.3760/cma.j.cn501113-20220228-00091.

ABSTRACT

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.

PMID:35462483 | DOI:10.3760/cma.j.cn501113-20220228-00091

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Divergent Signaling Pathways May Lead to Convergence in Cancer Therapy – A Review

Cell Physiol Biochem. 2022 Apr 25;56(2):180-208. doi: 10.33594/000000512.

ABSTRACT

Cancer is a chaos of uncontrolled cell proliferation that has consistently invented new circuitry programs to operate inside the cell machinery. Globally, cancer statistics account for 65% of mortality worldwide, mainly due to the adoption of lifestyle behaviours. In 2020, FDA approved 40 new drugs, out of which 16 (40%) were approved as cancer drugs. Overall, the risk of dying from cancer decreased, but further reductions in cancer death rates can be accelerated by applying existing cancer control knowledge across all the population segments, emphasising those in the lowest socio-economic and other disadvantaged population. Various therapeutic regimes, including low-molecular-weight inhibitors, targeting oncogenic signaling pathways are under development. However, the pitfall of targeted therapies is the quick emergence of acquired drug resistance encumbered with toxic side effects. Several FDA acclaimed therapeutic legacies or biosimilars earmarked signaling pathways of rare diseases (cystic fibrosis, erythropoietic protoporphyria, neuromyelitis optica spectrum disorder, tenosynovial giant cell tumor, sickle cell disease, systemic sclerosis-associated interstitial lung disease, muscular dystrophy), neurological and psychiatric disorders, infectious diseases, heart, lung, circulatory, endocrine diseases, autoimmune conditions, cancers and blood disorders. When cancer progresses, these signals develop specific characteristics that can be targeted for anti-cancer therapy. The designer inhibitors have emerged as novel pharmaceutical interventions that aim to block the pathways in an effort to reverse the abnormal phenotype of the cancer cells. Numerous cell-signaling channels have evolved and invigorated to make off three-dimensional feedback networks. The magnitude of accessible information by pathways occupies curated information as a consortium. To fully appreciate the pivotal roles that signaling cascades play in tumor development, it is necessary to understand the involved signaling cascades in the interaction between cancer cells. The prime endeavour is to canonically curate all signaling pathways involving cell cycle, EGFR, MAPK, GPCR, PI3K/ AKT/mTOR, immune checkpoints, nuclear receptors, janus kinase, transcription activators etc., involving the manipulation of genetic and nuclear receptors. Here, we will summarize the vast amount of information describing the signals that mediate crosstalk between cancer cells and the targets related to this crosstalk.

PMID:35462471 | DOI:10.33594/000000512

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Cut-off values of neonatal lysosomal storage disease-related enzymes detected by tandem mass spectrometry

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Mar 25;50(7):1-5. doi: 10.3724/zdxbyxb-2022-0095. Online ahead of print.

ABSTRACT

To establish cut-off values of lysosomal storage disease (LSD)-related enzymes by tandem mass spectrometry. A total of 26 689 newborns and 7 clinically confirmed LSD children underwent screening for LSDs (glycogen storage disease typeⅡ, Fabry disease, mucopolysaccharidosis type Ⅰ, Krabbe disease, Niemann-Pick disease A/B and Gaucher disease). The activities of LSD-related enzymes were detected by tandem mass spectrometry. The 20% of the median enzyme activity of each batch of acid β-glucocerebrosidase, acid sphingomyelinase, β-galactocerebroside, α–iduronidase and acid α-glucosidase, and the 30% of the median enzyme activity of were taken as cut-off values of corresponding enzymes. The genetic diagnosis was performed in neonates whose enzyme activity was lower than 70% of the cut-off value. The enzyme activities of 7 clinically confirmed cases were all lower than the cut-off values. Among 26 689 newborns, 142 cases (0.53%) were suspected positive for LSDs, including 25 cases of β-galactocerebroside deficiency, 1 case of α–iduronidase deficiency, 19 cases of α-galactosidase deficiency, and 97 cases of acid α-glucosidase deficiency. Eight infants were genetically diagnosed with LSDs, including 3 cases of glycogen storage disease type Ⅱ, 3 cases of Krabbe disease, and 2 cases of Fabry disease, with a positive predictive value of about 5.6%. Cut-off values ​​of the six LSD enzyme activities all showed a downward trend from March to August, and an upward trend from September to December. There was a statistically significant difference in LSD enzyme activity among different months (<0.05). The established cut-off values of LSD-related enzyme activities detected by tandem mass spectrometry can be used for screening LSDs in neonates, and the enzyme activity would be affected by temperature and humidity.

PMID:35462462 | DOI:10.3724/zdxbyxb-2022-0095

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Trends and influencing factors of perinatal birth defects in Huai’an from 2008 to 2020

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2021 Mar 25;50(7):1-9. doi: 10.3724/zdxbyxb-2021-0120. Online ahead of print.

ABSTRACT

: To analyze the incidence, trends and related factors of birth defects in Huai’an from 2008 to 2020. : The surveillance data from maternal and child health system of Huai’an from 2008 to 2020 and Huai’an Statistical Yearbook were used for analysis. Taking the annual change percentage and average annual change percentage (AAPC) as the main outcome indicators, the JoinPoint regression analysis was performed to estimate the changing trend of birth defects from 2008 to 2020. Spearman correlation analysis was used to examine the association between birth defects and birth rate, marriage rate, proportion of women with advanced maternal age. : During 2008 to 2020, a total of 3414 cases of neonatal birth defects occurred in Huai’an, with an incidence of 4.6‰ (3414/736 608). The rate of perinatal birth defects in Huai’an showed an increasing trend (AAPC=8.8%, =3.2, <0.01), and the year of 2016 was a significant changing point. Among 24 types of birth defects, the incidence of congenital heart disease rose and became the most prevalent defect, while the incidence of neural tube malformations such as anencephaly, encephalocele and spina bifida was declined. The incidence of birth defect was negatively correlated with the birth rate (=-0.751, <0.01), not correlated with marriage rate (=-0.516, >0.05), and positively correlated with the proportion of women with advanced maternal age (=0.726, <0.01). : The incidence of birth defects in Huai’an shows an increasing trend from 2008 to 2020 with congenital heart disease as the most common type of birth defect, and the increase of birth defects incidence is closely related with the increase of the proportion of women with advanced maternal age.

PMID:35462467 | DOI:10.3724/zdxbyxb-2021-0120

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Comparative efficacy of targeted structural patterns of electroencephalography neurofeedback in children with inattentive or combined attention deficit hyperactivity disorder

Brain Behav. 2022 Apr 24:e2572. doi: 10.1002/brb3.2572. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate and compare the effects of three courses of different structural patterns of electroencephalography neurofeedback on predominantly inattentive attention deficit hyperactivity disorder (ADHD-PI) and combined ADHD (ADHD-CT).

METHODS: Thirty-eight ADHD-PI and ADHD-CT children were selected and completed three courses of different structural patterns of electroencephalography neurofeedback according to their ADHD type. Before and after each course, relative power value of electroencephalography, including θ, β, α, SMR and their ratios (θ/β, θ/α), and eighteen integrated visual and auditory continuous performance test (IVA/CPT) quotients were obtained and compared. Data were analyzed by SPSS software, and p < .05 was considered statistically significant.

RESULTS: After one course, θ, three IVA/CPT quotients in both types and two comprehensive quotients in ADHD-CT changed significantly (all p < .05). After two courses, θ/α, θ/β and five IVA/CPT quotients in both types, θ and α in ADHD-PI, four comprehensive quotients, and four respond control quotients in ADHD-CT varied significantly compared to before treatment and after one course (all p < .05). After three courses, α, β, θ, θ/α, θ/β and ten IVA/CPT quotients in both types changed significantly compared to before treatment and after one course (all p < .05). In addition, six IVA/CPT quotients in both types after three courses were significantly higher than those after two courses (all p < .05).

CONCLUSION: Different structural patterns of electroencephalography neurofeedback targeted for ADHD-CT and ADHD-PI were both effective and feasible. Three courses of EEG neurofeedback were most effective.

PMID:35462456 | DOI:10.1002/brb3.2572

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Proteomic profiling of human bone from different anatomical sites – A pilot study

Proteomics Clin Appl. 2022 Apr 24:e2100049. doi: 10.1002/prca.202100049. Online ahead of print.

ABSTRACT

PURPOSE: The study aim is a comparative proteome-based analysis of different autologous bone entities (alveolar bone (AB), iliac cortical bone (IC) and iliac spongiosa (IS)) used for alveolar onlay grafting.

EXPERIMENTAL DESIGN: Site-matched bone samples of AB, IC and IS were harvested during alveolar onlay grafting. Proteins were extracted using a detergent-based (sodium dodecyl sulfate) strategy and trypsinized. Proteome analysis was performed using liquid chromatography – tandem mass spectrometry (LC-MS/MS). MaxQuant was used for peptide-to-spectrum matching, peak detection, and quantitation. Linear models for microarray analysis (LIMMA) were used to detect differentially abundant peptides and proteins.

RESULTS: 1730 different proteins were identified across the 15 samples at a false discovery rate of 1 %. Partial least-squares discriminant analysis approved segregation of AB, IC and IS protein profiles. LIMMA statistics highlighted 66 proteins that were more abundant in AB then in IC (vs. 92 proteins were enriched in IC over AB). Gene ontology enrichment analysis revealed a matrisomal vs. an immune-related proteome fingerprint in AB vs IC.

CONCLUSION AND CLINICAL RELEVANCE: This pilot study demonstrates an ECM protein-related proteome fingerprint in AB and an immune-related proteome fingerprint in IS and IC. This article is protected by copyright. All rights reserved.

PMID:35462455 | DOI:10.1002/prca.202100049

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Production and optimization of L-asparaginase by Streptomyces koyangensis SK4 isolated from Arctic sediment

J Basic Microbiol. 2022 Apr 24. doi: 10.1002/jobm.202200116. Online ahead of print.

ABSTRACT

Actinomycetes isolated from the Arctic sediment were evaluated for the production of the enzyme L-asparaginase, an enzyme used to treat acute lymphoblastic leukemia. The most potent strain Streptomyces koyangensis SK4 was selected for L-asparaginase enzyme production by submerged fermentation. The effect of various fermentation parameters on enzyme production was analyzed statistically using the Plackett Burman design and response surface method. Effects of eight parameters including temperature, pH, incubation time, inoculum size, agitation speed, the concentration of starch, L-asparagine and yeast extract were studied on L-asparaginase production by the Arctic isolate Streptomyces koyangensis SK4. Factors such as temperature, pH, incubation time, agitation speed and L-asparagine concentration were found to be important factors influencing the L-asparaginase production. Maximum enzyme activity of 136 IU/ml was obtained at 20°C on the seventh day of incubation in the Asparagine dextrose broth maintained at pH-7.5, agitation speed-125 rpm and L-asparagine concentration of 7.5 g/L. The statistical optimization method described in this study proved effective for increasing the L-asparaginase production by Arctic actinomycetes. This article is protected by copyright. All rights reserved.

PMID:35462434 | DOI:10.1002/jobm.202200116