Clinical Efficacy of Chemotherapy Regimen Combined with Levofloxacin in Patients with Pulmonary Tuberculosis Complicated with Type-2 Diabetes.

Objective: To evaluate the clinical efficacy of a chemotherapy regimen combined with levofloxacin in patients with pulmonary tuberculosis complicated with Type-2 diabetes. Methods: Total 80 patients with pulmonary tuberculosis complicated with Type-2 diabetes admitted to Baoding People's Hospital from January, 2019 to January, 2022 were randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. Patients in the control group were given the conventional 2HRZE/10HRE regimen, while those in the experimental group were given the chemotherapy regimen 2HRZEL/6HRE combined with levofloxacin. Sixty four slice spiral CT was used for chest plain scan before and after treatment, respectively, to evaluate the absorption of lesions based on the range of lung lesions; Venous blood was drawn to detect the changes of oxidative stress indicators, the incidence of adverse drug reactions and the negative conversion rate of sputum tuberculosis bacteria in the two groups. Results: After treatment, the efficacy of the experimental group was 90%, which was significantly higher than that of the control group (67.5%), with a statistically significant difference (p=0.01). After treatment, CD3+, CD4+, CD4+/CD8+ and other indicators in the experimental group were significantly higher than those in the control group, with a statistically significant difference (CD3+, p=0.01; CD4+, p=0.01; CD4+/CD8+, p=0.00), while CD8+ did not change significantly (p=0.92); The incidence of adverse reactions was 52.5% in the experimental group and 47.5% in the control group, with no statistically significant difference (p=0.66); The negative conversion rate of patients in the experimental group was significantly higher than that in the control group at one month, three months and six months after treatment, with a statistically significant difference (p<0.05). Conclusion: Chemotherapy combined with levofloxacin is a safe and effective regimen for patients' pulmonary tuberculosis complicated with Type-2 diabetes, boasting a variety of benefits such as improved clinical efficacy, ameliorated cellular immune status, a high negative conversion rate of sputum tuberculosis bacteria, and no significant increase in adverse reactions.

Four New ent-Kaurane Diterpene Glycosides from Isodon henryi.

To obtain diterpene glycosides from an aqueous extract of the aerial parts of Isodon henryi and further investigate their cytotoxicities, in this study, a total of seven compounds were isolated, including six ent-kaurane diterpene glycosides (1-6) and one diterpene aglycon (7). Among the seven ent-kaurane diterpenes obtained, four were novel compounds, including ent-7,20-epoxy- kaur-16-en-1α,6ß,7ß,15ß-tetrahydroxyl-11-O-ß-d-glucopyranoside (1), ent-7,20-epoxy-kaur-16-en- 6ß,7ß,14ß,15ß-tetrahydroxyl-1-O-ß-d-glucopyranoside (2), ent-7,20-epoxy-kaur-16-en-6ß,7ß,15ß- trihydroxyl-1-O-ß-d-glucopyranoside (3), and ent-7,20-epoxy-kaur-16-en-7ß,11ß,14α,15ß-tetrahydr- oxyl-6-O-ß-d-glucopyranoside (4), and three were isolated from this plant for the first time (5-7). Their structures were elucidated by utilizing spectroscopic methods and electronic circular dichroism analyses. Furthermore, the cytotoxicities of all seven compounds were investigated in four human cancer cell lines, including A2780, BGC-823, HCT-116, and HepG2. The IC50 values of these diterpenes ranged from 0.18 to 2.44 mM in the tested cell lines. In addition, the structure-cytotoxicity relationship of diterpene glycosides was also evaluated to study the effect of glycosylation on the cytotoxicity of diterpene compounds.

[Studies on chemical constituents of Isodon henryi].

The chemical constituents of the water extraction of the aerial parts of Isodon henryi were investigated by various chromatographic methods including D-101 macroporous adsorptive resins,silica gel,sephadex LH-20,and semi-preparative HPLC. As a result,ten compounds were separated and purified. By analyses of the UV,IR,MS,NMR spectra,their structures were determined as rabdosinate( 1),lasiokaurin( 2),epinodosinol( 3),rabdosichuanin C( 4),epinodosin( 5),hebeirubescensin k( 6),rubescensin C( 7),enmenol( 8),oridonin( 9),and enmenol-1-ß-glucoside( 10). Compounds 1-8 and 10 were isolated from I. henryi for the first time. Compounds 2 and 9 showed inhibitory effects against four tumor cells,with IC50 values of 2. 25-9. 32 µmol·L-1.

Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry.

OBJECTIVE: To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms. METHODS: Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD). RESULTS: MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD. CONCLUSIONS: MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Alkbh1-mediated DNA N6-methyladenine modification regulates bone marrow mesenchymal stem cell fate during skeletal aging.

OBJECTIVES: DNA N6-methyladenine (N6-mA) demethylase Alkbh1 participates in regulating osteogenic differentiation of mesenchymal stem cell (MSCs) and vascular calcification. However, the role of Alkbh1 in bone metabolism remains unclear. MATERIALS AND METHODS: Bone marrow mesenchymal stem cells (BMSCs)-specific Alkbh1 knockout mice were used to investigate the role of Alkbh1 in bone metabolism. Western blot, qRT-PCR, and immunofluorescent staining were used to evaluate the expression of Alkbh1 or optineurin (optn). Micro-CT, histomorphometric analysis, and calcein double-labeling assay were used to evaluate bone phenotypes. Cell staining and qRT-PCR were used to evaluate the osteogenic or adipogenic differentiation of BMSCs. Dot blotting was used to detect the level of N6-mA in genomic DNA. Chromatin immunoprecipitation (Chip) assays were used to identify critical targets of Alkbh1. Alkbh1 adeno-associated virus was used to overexpress Alkbh1 in aged mice. RESULTS: Alkbh1 expression in BMSCs declined during aging. Knockout of Alkbh1 promoted adipogenic differentiation of BMSCs while inhibited osteogenic differentiation. BMSC-specific Alkbh1 knockout mice exhibited reduced bone mass and increased marrow adiposity. Mechanistically, we identified optn as the downstream target through which Alkbh1-mediated DNA m6A modification regulated BMSCs fate. Overexpression of Alkbh1 attenuated bone loss and marrow fat accumulation in aged mice. CONCLUSIONS: Our findings demonstrated that Alkbh1 regulated BMSCs fate and bone-fat balance during skeletal aging and provided a potential target for the treatment of osteoporosis.

Mutated lncRNA increase the risk of type 2 diabetes by promoting ß cell dysfunction and insulin resistance.

Islet ß cell dysfunction and insulin resistance are the main pathogenesis of type 2 diabetes (T2D), but the mechanism remains unclear. Here we identify a rs3819316 C > T mutation in lncRNA Reg1cp mainly expressed in islets associated with an increased risk of T2D. Analyses in 16,113 Chinese adults reveal that Mut-Reg1cp individuals had higher incidence of T2D and presented impaired insulin secretion as well as increased insulin resistance. Mice with islet ß cell specific Mut-Reg1cp knock-in have more severe ß cell dysfunction and insulin resistance. Mass spectrometry assay of proteins after RNA pulldown demonstrate that Mut-Reg1cp directly binds to polypyrimidine tract binding protein 1 (PTBP1), further immunofluorescence staining, western blot analysis, qPCR analysis and glucose stimulated insulin secretion test reveal that Mut-Reg1cp disrupts the stabilization of insulin mRNA by inhibiting the phosphorylation of PTBP1 in ß cells. Furthermore, islet derived exosomes transfer Mut-Reg1cp into peripheral tissue, which then promote insulin resistance by inhibiting AdipoR1 translation and adiponectin signaling. Our findings identify a novel mutation in lncRNA involved in the pathogenesis of T2D, and reveal a new mechanism for the development of T2D.

Clinical features and risk factors of severely and critically ill patients with COVID-19.

BACKGROUND: As of June 1, 2020, over 370000 coronavirus disease 2019 (COVID-19) deaths have been reported to the World Health Organization. However, the risk factors for patients with moderate-to-severe or severe-to-critical COVID-19 remain unclear. AIM: To explore the characteristics and predictive markers of severely and critically ill patients with COVID-19. METHODS: A retrospective study was conducted at the B11 Zhongfaxincheng campus and E1-3 Guanggu campus of Tongji Hospital affiliated with Huazhong University of Science and Technology in Wuhan. Patients with COVID-19 admitted from 1st February 2020 to 8th March 2020 were enrolled and categorized into 3 groups: The moderate group, severe group and critically ill group. Epidemiological data, demographic data, clinical symptoms and outcomes, complications, laboratory tests and radiographic examinations were collected retrospectively from the hospital information system and then compared between groups. RESULTS: A total of 126 patients were enrolled. There were 59 in the moderate group, 49 in the severe group, and 18 in the critically ill group. Multivariate logistic regression analysis showed that age [odd ratio (OR) = 1.055, 95% (confidence interval) CI: 1.099-1.104], elevated neutrophil-to-lymphocyte ratios (OR = 4.019, 95%CI: 1.045-15.467) and elevated high-sensitivity cardiac troponin I (OR = 10.126, 95%CI: 1.088 -94.247) were high-risk factors. CONCLUSION: The following indicators can help clinicians identify patients with severe COVID-19 at an early stage: age, an elevated neutrophil-to-lymphocyte ratio and high sensitivity cardiac troponin I.

Antcin A, a steroid-like compound from Antrodia camphorata, exerts anti-inflammatory effect via mimicking glucocorticoids.

AIM: To determine the active ingredient of Niuchangchih (Antrodia camphorata) responsible for its anti-inflammatory effects and the relevant molecular mechanisms. METHODS: Five major antcins (A, B, C, H, and K) were isolated from fruiting bodies of Niuchangchih. Structural similarity between the antcins and 2 glucocorticoids (cortisone and dexamethasone) was compared. After incubation with each compound, the cytosolic glucocorticoid receptor (GR) was examined for its migration into the nucleus. Mo lecular docking was performed to model the tertiary structure of GR associated with antcins. RESULTS: Incubation with cortisone, dexamethasone or antcin A (but not antcins B, C, H, and K) led to the migration of glucocorticoid receptor into the nucleus. The minimal concentration of antcin A, cortisone and dexamethasone to induce nuclear migration of glucocorticoid receptor was 10, 1, and 0.1 mol/L, respectively. The results are in agreement with the simulated binding affinity scores of these three ligands docking to the glucocorticoid receptor. Molecular modeling indicates that C-7 of antcin A or glucocorticoids is exposed to a hydrophobic region in the binding cavity of the glucocorticoid receptor, and the attachment of a hydrophilic group to C-7 of the other four antcins presumably results in their being expelled when docking to the cavity. CONCLUSION: The anti-inflammatory effect of Niuchangchih is, at least, partly attributed to antcin A that mimics glucocorticoids and triggers translocation of glucocorticoid receptor into nucleus to initiate the suppressing inflammation.

Identification of the function and mechanism of m6A reader IGF2BP2 in Alzheimer's disease.

Alzheimer's disease, the most common form of dementia in the elderly, is a kind of neurodegenerative disease. However, its pathogenesis and diagnosis remain unclear. M6A is related to nervous system development and neurodegenerative diseases. Here in this study, using multiple RNA-seq datasets of Alzheimer's brain tissues, along with bioinformatic analysis, we innovatively found that m6A reader protein IGF2BP2 was abnormally highly expressed in Alzheimer's patients. After compared between Alzheimer's and normal brain samples, and between IGF2BP2- high and IGF2BP2- low subgroups of Alzheimer's patients, we took the shared differentially expressed genes as the relevant gene sets of IGF2PB2 affecting Alzheimer's disease occurrence for subsequent analysis. Then, weight gene correlation analysis was conducted and 17 functional modules were identified. The module that most positively correlated with Alzheimer's disease and IGF2PB2-high subgroups were mainly participated in ECM receptor interaction, focal adhesion, cytokine-cytokine receptor interaction, and TGF-beta signaling pathway. Afterwards, a hub gene-based model including 20 genes was constructed by LASSO regression and validated by ROC curve for Alzheimer diagnosis. Finally, we preliminarily elucidated that IGF2BP2 could bind with mRNAs in a m6A-dependent manner. This study first elucidates the pathogenic role of IGF2BP2 in Alzheimer's disease. IGF2BP2 and its relevant m6A modifications are potential to be new diagnostic and therapeutic targets for Alzheimer's patients.

A new ent-kaurane diterpene from Isodon henryi.

One new ent-Kaurane diterpenoid (1) was isolated from the ethyl acetate fraction of Isodon henryi. Along with ten diterpenoids (2-11) were isolated from this plant for the first time, including six 7,20-epoxy diterpenoids, three enmenol-type diterpenoids and one 6,7-seco-ent-kaurene diterpenoid. Their structures were elucidated by 1 D and 2 D NMR, confirmed by HRESIMS and electronic circular dichroism analyses. Furthermore, the cytotoxicities of twelve compounds were investigated in five human cancer cell lines, including A2780, BGC-823, HCT-116, HepG2 and HeLa. And the IC50 values of these diterpenoids ranged from 2.1 to 88.8 µM in the tested cell lines. Based on the molecular structures of 12 compounds and the bioassay results, it suggests that α,ß-unsaturated pentanone is the cytotoxic active site of 7,20 epoxy ent-kaurane diterpenoid, but it does not contribute much to enmenol-type diterpenoid.Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1675067.

Two new sesquiterpenoid glycosides from the stems of Zanthoxylum armatum DC.

Two new sesquiterpenoid glycosides as dihydrophaseic acid 4'-O-[6″-O-(4″'-hydroxy-3″', 5″'-dimethoxy) benzoyl)]-ß-D-glucopyranoside (1) and dihydrophaseic acid 4'-O-[6″-O-(3″'-methoxy- 4″'-hydroxy) benzoyl)]-ß-D-glucopyranoside (2), were isolated from the stems of Zanthoxylum armatum in the study. The compound 1 and 2 showed moderate scavenging activity in DPPH free radical assay with IC50 values of 241 and 264 µM, respectively.

Use of Low-Dose Recombinant Factor â ¦a for Uncontrolled Perioperative Bleeding.

BACKGROUND: Recombinant activated factor VIIa (rFVIIa) is a prohemostatic agent initially approved for use in hemophilia patients and has also been used for a diverse range of off-label indications in the context of massive uncontrolled blood loss; however, no convincing evidence exists regarding the optimal dose of rFVIIa to treat uncontrolled bleeding in surgical patients. AIM: To evaluate the effects and safety of a very low dose of rFⅦa in patients with uncontrolled perioperative bleeding in the surgical intensive care unit (ICU). METHODS: 55 patients from Beijing Hospital, who received rFⅦa between July 2004 and November 2018 for uncontrolled perioperative bleeding were included. The controls were matched for age, sex, severity, and operation type. The baseline demographics, survival, changes in bleeding and transfusion, coagulation parameters and complications were analyzed. RESULTS: A low dose of rFⅦa (2.0∼3.6 mg, with a median dose of 39.02 µg/kg) appears to be effective in controlling massive hemorrhage (with an effective rate of 74.55%), and can reduce volume of red blood cell transfusion, improve coagulation status, while has a relatively low risk of thromboembolic complications (3.6%). CONCLUSION: In patients with uncontrolled perioperative bleeding, a low dose of rFⅦa could be used when traditional methods are ineffective.

[Influence of the venous catheter site on data of pulse indicator continuous cardiac output monitoring].

OBJECTIVE: To compare the use of subclavian vein catheter and femoral vein catheter, in monitoring pulse indicator continuous cardiac output (PiCCO) monitoring data cardiac index (CI), extravascular lung water index (EVLWI), and global end-diastolic volume index (GEDVI) with central venous injection of the bolus cold saline injection, in order to determine whether the femoral vein access, which is not typically used, could be used to obtain reliable data. METHODS: Thirteen patients in Beijing Hospital intensive care unit (ICU) were involved, from January 2007 to March 2009. Each patient was monitored with PiCCOplus device, after an injection of cold saline bolus via both femoral and subclavian venous catheter. Paired t-test and Bland-Altman analysis were used to compare CI, EVLWI and GEDVI values. RESULTS: Data of 39 measurements were collected. The bias between femoral injection and subclavian injection were CI (0.28+/-0.46) L x min(-1) x m(-2), EVLWI (1.05+/-1.89) ml/kg, GEDVI (195.2+/-105.7) ml/m(2), and they were statistically significant (P values was 0.000 5, 0.001 3, <0.0001, respectively). The Bland-Altman analysis showed an clinically overestimation of GEDVI after femoral injection (limit of concordance was -11.9, 402.3), compared with that after subclavian injection. CONCLUSION: Measurements with a cold saline bolus via a femoral catheter, compared to those via a subclavian catheter, lead to overestimation of CI, EVLWI and GEDVI values, and a great bias of GEDVI should be taken into account in clinical work.

[Significance of Bone Marrow Unclassifiable Cells in Diagnosis of Fever of Unknown Origin].

OBJECTIVE: To investigate the clinical significance of bone marrow unclassifiable cells in diagnosis of fever of unknown origin(FUO). METHODS: The clinical data of 60 patients with FUO admitted in the first affiliated hospital of Xi'an Jiaotong university from June 2014 to May 2016 were collected, and 60 patients with FUO were divided into 2 group: group A(30 cases) in which the unclassifiable cells in bone marrow were observed by bone marrow examination, and group B(30 cases) in which the unclassifiable cells in bone marrow not were found by bone marrow examination. The clinical characteristics, bone marrow features, immunophenotypes of bone marrow cells and prognosis of patients in 2 groups were analyzed retrospectively. RESULTS: Out of 30 patients in group A, 18 were diagnosed as malignant tumors including 12 cases of lymphoma, while out of 30 patients in group B, 5 cases were diagnosed as malignant tumor, including 3 cases of lymphoma. For the patients with non-tumor diseases, the bone marrow unclassifiable cells disappeared after the patients condition was improved. CONCLUSION: The bone marrow examination including the smear and biopsy shonld be performed routinely for the patients with FUO. If the unclassifiable cells are observed morphologically in bone marrow of patients with FUO, the disease of patients should be considered as malignant tumor, especially, lymphoma.

Small RNA sequencing reveals dynamic microRNA expression of important nutrient metabolism during development of Camellia oleifera fruit.

To obtain insight into the function of miRNAs in the synthesis and storage of important nutrients during the development of Camellia oleifera fruit, Illumina sequencing of flower and fruit small-RNA was conducted. The results revealed that 797 miRNAs were significantly differentially expressed between flower and fruit samples of Camellia oleifera. Through integrated GO and KEGG function annotations, it was determined that the miRNA target genes were mainly involved in metabolic pathways, plant hormone signal transduction, fruit development, mitosis and regulation of biosynthetic processes. Carbohydrate accumulation genes were differentially regulated by miR156, miR390 and miR395 in the fruit growth and development process. MiR477 is the key miRNA functioning in regulation of genes and involved in fatty acid synthesis. Additionally, miR156 also has the function of regulating glycolysis and nutrient transformation genes.

[Study on safety and efficacy of concentrated potassium chloride infusions in critically ill patients with hypokalemia].

OBJECTIVE: To explore the safety and clinical efficacy of intravenous infusion of concentrated potassium chloride using micro-pumps in critically ill patients with hypokalemia. METHODS: One hundred and twenty-eight critically ill patients with hypokalemia, the endogenous creatinine clearance rate over 0.5 ml/second and the urine output over 50 ml/hour were randomly divided into the therapy group (n=64) and the control group (n=64). Patients in therapy group received 1,208 mmol/L (9%) KCl, while those in the control group received 201 mmol/L (1.5%) potassium chloride, intravenously with the aid of a micro-pump, with hourly equal quantity of KCl in both groups. Patients in both groups were monitored strictly, and the potassium infusion was stopped whenever the serum potassium exceeded or equal to 3.5 mmol/L. RESULTS: It took (15.55+/-3.22) hours and (14.18+/-4.93) hours for the therapy group and the control group to correct the hypokalemia respectively, and there was no significant difference (P>0.05). Potassium infusion brought larger amount of fluid in the control group than the therapy group [(124.36+/-25.79) ml vs. (680.83+/-236.70) ml, P<0.01]. All patients tolerated the infusion without evidence of hemodynamic change, hyperkalemia or acute heart dysfunction. For all the patients, renal function did not throw significant influence on the potassium infusion time. An inverse correlation was observed between preinfusion potassium concentration and the quantity of potassium infused (r= -0.259, P<0.01). CONCLUSION: Under meticulous monitoring, it is safe and effective to infuse concentrated potassium for the critically ill patients with hypokalemia. This strategy can also be followed in patients with mild renal dysfunction but without oliguria or anuria under careful monitoring.

Isolation and purification of diterpenoids from the aerial parts of Isodon excisoides target-guided by UPLC-LTQ-Orbitrap-MS.

Cytotoxic diterpenoids were enriched and orientation prepared from the aerial parts of Isodon excisoides target-guided by UPLC-LTQ-Orbitrap-MS. Four diterpenoids were obtained, including a novel compound: 1α-acetoxy-7α, 14ß, 20α-trihydroxy-ent-kaur-16-en-15-one (1); together with three known compounds kamebakaurin (2), lasiokaurin (3), enmenol-1-ß-glucoside (4). Their structures were elucidated on the basis of spectroscopic methods in conjunction with published data for their analogues. All compounds were tested for their cytotoxic effects against five human cancer cell lines HCT-116, HepG2, A2780, NCI-H1650 and BGC-823, respectively. Compounds 1 and 2 showed obviously cytotoxic activity against the five cancer cell lines with IC50 ranging from 1.06 to 3.60 µM. Compounds 3 and 4 showed selective cytotoxic activity.

Investigation on critical structural motifs of ligands for triggering glucocorticoid receptor nuclear migration through molecular docking simulations.

The glucocorticoid receptor (GR), a transcription factor regulating gene expression in a ligand-dependent fashion, is known for flexibility in adapting various ligands with their structures ranging from steroid to non-steroid. However, in our previous study, GR shows a stringent discrimination against a set of steroid ligands with highly similar structures for triggering its nuclear migration. In order to resolve this puzzle, we employed molecular docking simulations to investigate the origin of this structural discrimination. By analyzing the docking orientations and the related ligand-GR interaction patterns, we found that the hydrophilicity mismatch between the docking ligand and the GR ligand-binding site is the main cause combined with the steric hindrance and structural rigidness of these steroid ligands. Furthermore, we utilized this knowledge to rationalize how the structure-binding interaction of non-steroid ligands triggers GR nuclear migration with their structures available in Protein Data Bank.

Occult HBV Infection in Immunized Neonates Born to HBsAg-Positive Mothers: A Prospective and Follow-Up Study.

OBJECTIVE: Occult HBV infection (OBI) has been reported in infants born to HBsAg-positive mothers despite immunization. This study aims to determine the maintenance of this status in a prospective birth cohort. METHODS: A total of 158 neonates born to HBsAg-positive mothers were enrolled. All received passive-active immunization against HBV according to a 0-1-6 schedule. Sera were collected at 7 months of age. Those diagnosed with OBI were serially followed up at 12, 24 and 36 months of age. HBV serological markers were determined by Abbott i2000 system. HBV DNA was quantitated by Abbott m2000 system. Standard PCR followed by direct sequencing were applied for mother-child HBV pairs. Homology and phylogenetic comparisons were done by BLAST and Mega 5. RESULTS: All the 158 neonates were HBsAg-negative and anti-HBs-positive at 7 months of age, and 32 (20.3%) of them were diagnosed with OBI, with a median HBV DNA level of 1.97 (1.20-3.71) log IU/mL. Of them, HBV DNA was positive in 25.0%, 21.9% and 7.7% at 12, 24 and 36 months of age, respectively. HBV DNA disappeared at one of the follow-up points in 31 neonates, however, rebounded to low levels in 6 of them thereafter. HBV DNA persisted at low levels during follow-ups in the other one neonate apart from the above 31. All remained negative for HBsAg. Only two (6.3%) neonates were positive for anti-HBc after 24 months of age. HBV showed close homology and phylogenetic relationships for mother-child pairs. S-escape mutant, G145R, was not discovered. The first vaccine dose within 6 hours of birth significantly reduced the occurrence of OBI (59.4% vs. 83.3%, p = 0.003). CONCLUSIONS: HBV may be controlled in immunized neonates of HBsAg-positive mothers, after being diagnosed with OBI. Timely vaccination against HBV may provide the utmost protection. Long-term and close monitorings are needed.