[A real-world study on the features of postpartum hepatitis flares in pregnant women with chronic HBV infection].

Objective: To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection. Methods: A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data. Results: A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z = -1.981, P = 0.048), aspartate aminotransferase (AST, z = -3.956, P < 0.001), HBV load (z = -15.292, P < 0.001), and HBeAg (z = -4.77, P < 0.001) at delivery in patients who received medication and those who did not. All patients ALT, AST, total bilirubin, direct bilirubin, and albumin showed an upward trend within six weeks after delivery. A total of 231 cases developed hepatitis within 48 weeks after delivery. Among them, 173 cases first showed ALT abnormalities within six weeks postpartum. Conclusion: Hepatitis flare incidence peaked six weeks after delivery or six weeks after drug withdrawal in pregnant women with chronic HBV infection.

[Influence of implantable Collamer lens implantation on choroidal thickness and blood flow density].

Objective: To observe the impact of implantable Collamer lens (ICL) implantation surgery on choroidal thickness and blood flow density in myopic patients. Methods: This was a prospective cohort study. Patients undergoing ICL surgery at Qingdao University Affiliated Hospital between June 2021 and May 2023 were consecutively enrolled. Patients were categorized into high myopia (HM) and super high myopia (SHM) groups based on whether their spherical equivalence power exceeded 10.00 D. Comprehensive ophthalmic examinations, including optical coherence tomography, optical coherence tomography angiography, visual acuity assessment, intraocular pressure measurement, and optometry, were performed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Results: A total of 42 patients (84 eyes), with an average age of (25.27±3.18) years, comprising 11 males and 31 females, were enrolled in the study. Among them, 20 patients belonged to the HM group, while 22 patients were in the SHM group. Both choroidal thickness and blood flow density exhibited significant increases at postoperative 1 week and 1 month compared to preoperative levels (P<0.05), but returned to baseline levels by postoperative 3 months. Specifically, the subfoveal choroidal thickness increased from (169.49±61.57) µm preoperatively to (180.16±66.61) µm at 1 week, (186.69±63.32) µm at 1 month, and then reverted to (169.58±60.82) µm at 3 months. The central choroidal blood flow density showed changes from 60.03%±1.60% preoperatively to 61.04%±1.17% at 1 week, 60.42%±1.81% at 1 month, and 60.22%±1.57% at 3 months. Furthermore, the HM group exhibited more pronounced changes in both choroidal thickness and blood flow density across all time points compared to the SHM group. Significant differences were observed in choroidal thickness changes at various areas at 1 month, while changes in blood flow density in specific areas were significant. However, no significant differences were noted at 3 months postoperatively. Correlation analysis revealed a negative correlation of changes in subfoveal choroidal thickness and central choroidal blood flow density postoperatively at 1 week and 3 months with preoperative choroidal blood flow density. Notably, no correlation was found between preoperative choroidal thickness and postoperative changes. Conclusions: In the early period following ICL implantation, the increase in choroidal thickness and blood flow density may be more pronounced in HM compared to SHM, but the two parameters can return to baseline levels by 3 months. ICL implantation transiently affects the fundus microenvironment in myopic patients, with implications of preoperative choroidal blood flow.

Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum.

PURPOSE: Bone morphogenic proteins (BMPs) regulate gene expression that is related to many critical developmental processes, including osteogenesis for which they are named. In addition, BMP2 is widely expressed in cells of mesenchymal origin, including bone, cartilage, skeletal and cardiac muscle, and adipose tissue. It also participates in neurodevelopment by inducing differentiation of neural stem cells. In humans, BMP2 variants result in a multiple congenital anomaly syndrome through a haploinsufficiency mechanism. We sought to expand the phenotypic spectrum and highlight phenotypes of patients harboring monoallelic missense variants in BMP2. METHODS: We used retrospective chart review to examine phenotypes from an international cohort of 18 individuals and compared these with published cases. Patient-derived missense variants were modeled in zebrafish to examine their effect on the ability of bmp2b to promote embryonic ventralization. RESULTS: The presented cases recapitulated existing descriptions of BMP2-related disorders, including craniofacial, cardiac, and skeletal anomalies and exhibit a wide phenotypic spectrum. We also identified patients with neural tube defects, structural brain anomalies, and endocrinopathies. Missense variants modeled in zebrafish resulted in loss of protein function. CONCLUSION: We use this expansion of reported phenotypes to suggest multidisciplinary medical monitoring and management of patients with BMP2-related skeletal dysplasia spectrum.

[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

[Mechanical analysis of the impact of the morphology of the iris and ciliary body on the central vault after posterior chamber phakic intraocular lens implantation].

Objective: To investigate the impact of the iris and ciliary body morphology on the central vault after phakic posterior chamber intraocular lens (pIOL) implantation. Methods: This research was based on the retrospective analysis of 123 patients (123 eyes) who underwent pIOL implantation in the Department of Ophthalmology, Affiliated Hospital of Qingdao University between June 2018 and June 2020. The anterior segment structure was observed with an ultrasound biomicroscope before surgery, and all morphological parameters of the iris and ciliary body were measured manually using the ImageJ software, including iris span (IS), iris convexity (IC), iris-ciliary body contact distance (ICCD) and iris-lens contact distance (ILCD). The ICCD was divided into Q1, Q2 and Q3 groups according to the equidistant distance of 0.36 mm. The lens thickness was measured with the IOLMaster. The horizontal corneal diameter and anterior chamber depth were measured using the Pentacam. The central vaults were measured by optical coherence tomography at 1 week, 3 months and 1 year after surgery. The relationships between vault values and preoperative parameters of the anterior segment were evaluated using the Pearson correlation analysis, Spearman correlation analysis, and multiple linear regression. The repeated measures ANOVA was applied to identify changes of vault values over time. Results: The mean values of the vaults at 1 week, 3 months and 1 year after surgery were (723±265) µm, (642±255) µm and (613±280) µm, respectively. The difference among them was statistically significant (F=50.143, P<0.001). The vaults continued to decline within 1 year after pIOL implantation, and the total decline was (122±86) µm. The vaults declined by (69±98) µm from postoperative 1 week to 3 months and by (52±54) µm from postoperative 3 months to 1 year. The regression formula showed that the pIOL size and ILCD were positively related with the vault, while the LT, IS and IC were negatively related with the vault at 1 week postoperatively (adjusted R²=0.404, P<0.001). The pIOL size and ILCD were positively related with the vault, while the IS and IC were negatively related with the vault at 3 months postoperatively (adjusted R²=0.342, P<0.001). The pIOL size was positively related with the vault, while the IS and IC were negatively related with the vault at 1 year postoperatively (adjusted R²=0.661, P<0.001). The vault values were higher in group Q3 compared to group Q1 at every timepoint, and the vault value was higher in group Q2 compared to Q1 at 1 year postoperatively. Conclusions: In the early postoperative period, eyes with a larger pIOL, shorter iris span, longer contact distance between the iris and ciliary body, and longer contact distance between the iris and lens were associated with a higher rate of excessive vaults. Meanwhile, eyes with a thicker lens and larger iris reverse convexity were more likely to obtain insufficient vaults. Within one year after surgery, the pIOL size, IS, IC and ICCD continued to impact on the vault. The ICCD, ILCD and IC can reflect the posterior chamber volume and change the haptic location and force, thus affecting the vault.

Imaging features of synovial chondromatosis of the temporomandibular joint: a report of 34 cases.

AIM: To investigate the imaging features of synovial chondromatosis of the temporomandibular joint (TMJ), which is a rare benign arthropathy with cartilaginous proliferation. MATERIALS AND METHODS: Computed tomography and magnetic resonance imaging examinations of 34 patients with histopathologically confirmed primary synovial chondromatosis of the TMJ were reviewed retrospectively. Imaging features including the lesion epicentre, destruction/sclerosis of surrounding bone, calcification, periosteal reaction, osteophyte, lesion size, and joint space dimensions were assessed. RESULTS: Thirty-one of thirty-four patients (91.2%) showed the superior joint space as the lesion epicentre. For the mandibular condyle, more than one-third of patients (14/34; 41.2%) showed no destruction, and more than half of patients (19/34; 55.9%) showed no sclerosis. Conversely, >70% of patients showed destruction and sclerosis of the articular eminence/glenoid fossa, while >80% of patients (28/34; 82.4%) presented with various calcifications, including the ring-and-arc (9/34; 26.5%) and popcorn (13/34; 38.2%) types. The mean joint space on the affected side was significantly larger than that of the unaffected side (p<0.001). More than three-fourths of patients (76.9%) experienced no interval increase in lesion size during an average of 1.6 years of follow-up. CONCLUSION: Synovial chondromatosis of the TMJ demonstrated several imaging features, including the lesion centre being located in the superior joint space, resultant articular eminence/glenoid fossa-oriented bone changes, ring-and-arc and popcorn calcification, joint space widening, and self-limiting growth. These imaging features may be helpful in differentiating synovial chondromatosis from other lesions of the TMJ.

Effect modification of the association between diurnal temperature range and hospitalisations for ischaemic stroke by temperature in Hefei, China.

OBJECTIVES: Diurnal temperature range (DTR) is an important indicator of global climate change. Many epidemiological studies have reported the associations between high DTR and human health. This study investigated the association between DTR and hospitalisations for ischaemic stroke in Hefei, China. STUDY DESIGN: This is an ecological study. METHODS: Data of daily hospital admissions for ischaemic stroke and meteorological variables from 1 January 2009 to 31 December 2017 were collected in Hefei, China. A generalised additive model combined with distributed lag non-linear model was used to quantify the effects of DTR on ischaemic stroke. The interactive effect between DTR and temperature was explored with a non-parametric bivariate response surface model. RESULTS: High DTR was associated with hospitalisations for ischaemic stroke. The adverse effect of extremely high DTR (99th percentile [17.1 °C]) occurred after 8 days (relative risk [RR] = 1.021, 95% confidence interval [CI] = 1.002, 1.041) and the maximum effect appeared after 12 days (RR = 1.029, 95% CI = 1.011, 1.046). The overall trend of the effect of DTR on ischaemic stroke was decreasing. In addition, there was a significant interactive effect of high DTR and low temperature on ischaemic stroke. CONCLUSIONS: This study suggests that the impact of high DTR should be considered when formulating targeted measures to prevent ischaemic stroke, especially for those days with high DTR and low mean temperature.

[Long-term rituximab treatment of refractory idiopathic inflammatory myopathy: A report of 3 cases].

Idiopathic inflammatory myopathies are a group of rare but serious diseases. The treatment of refractory idiopathic inflammatory myopathy is always challenging, especially in children. Three cases of refractory idiopathic inflammatory myopathy treated by rituximab were reported and discussed with the review of relevant literature. All were female with on-set age of 8 years and 6 months, 11 years and 7 months, 4 years and 2 months old, respectively. All had acute onset, presenting with progressive and severe muscle weakness. All lost ambulation within 1 or 2 months, with difficult swallowing and low voice. Respiratory distress occurred in case 2 after an attack of asphyxia due to an aspiration of sputum, and ventilator support was required for 1 month. Rashes were detected at the initial stage of the disease in cases 2 and 3. Patient 2 showed facial erythematous papules, spreading to her neck and hands. Patient 3 showed purplish eyelids with peri-orbital swelling, generalized edema involving all her limbs. Creatine kinase (CK) levels were markedly elevated in all the patients, ranging from 6 000 IU/L to 28 819 IU/L. Anti-SRP antibody was identified in cases 1, and anti-NXP2 antibodies were confirmed in cases 2 and 3. MRI of both thighs in all the patients showed profound muscle and fascial edema. Muscle pathology of patient 1 showed prominent fiber variation and endomysial fibrosis, with overexpression of MHC-Ⅰ. While muscle pathology in patients 2 and 3 showed scattered fiber necrosis, regeneration, endomysial edema without inflammatory cell infiltration. All the patients were diagnosed with idiopathic inflammatory myopathy and failed to the initial treatment including adequate glucocorticoids and high-dose immunoglobulin therapy. Other immunosuppressants (methotrexate, cyclophosphamide) were also tried in cases 2 and 3 with poor response. Then all the patients were treated with rituximab combined with glucocorticoids. Patient 1 regained normal strength and discontinued rituximab at the end of her last follow-up (2 years and 7 mouths). Though calcinosis developed during the follow-up period, significant improvement was noticed in cases 2 and 3 (both regained the ability to walk independently) at the end of their last follow-up after 2 years and 8 months, 3 years and 2 months respectively. Long-term rituximab therapy may improve the prognosis of refractory idiopathic inflammatory myopathy, especially with positive anti-SRP and anti-NXP2 antibodies.

Imaging features of chondrosarcoma of the temporomandibular joint: report of nine cases and literature review.

AIM: To investigate the imaging features of chondrosarcoma of the temporomandibular joint (TMJ) and review the literature. MATERIALS AND METHODS: Computed tomography (CT), magnetic resonance imaging (MRI), and integrated positron-emission tomography (PET)/CT images of nine patients with histopathologically confirmed chondrosarcoma of the TMJ were reviewed retrospectively. Imaging features regarding the direction of lesion growth, bone destruction, infiltration into the tendon of the lateral pterygoid muscle (LPM) in the pterygoid fovea, enhancement pattern, calcification, periosteal reaction, markedly hyperintense T2 signal area, and qualitative PET signal intensity were evaluated. RESULTS: Seven of nine patients (77.8%) presented with lesion growth that was outward from the medulla of the mandibular condyle. Infiltration into the tendon of LPM in the pterygoid fovea was observed in all cases, and 77.8% (7/9) of them demonstrated >50% infiltration. All the lesions showed a mixed peripheral and internal enhancement, and revealed a markedly hyperintense T2 signal intensity area, which showed no enhancement. Although five of nine cases demonstrated higher FDG uptake compared with that of the liver, the other four cases showed less FDG uptake than that of the liver. CONCLUSION: Chondrosarcoma of the TMJ demonstrated several imaging features, including outward growth from the mandibular condyle, resultant infiltration into the tendon of LPM in the pterygoid fovea, various patterns of internal enhancement, and a markedly hyperintense T2 signal intensity area. These imaging features may be helpful to differentiate chondrosarcoma from other lesions of the TMJ.

Imperatorin ameliorates learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling in prenatally-stressed female offspring.

Prenatal stress (PS) can lead to impaired spatial learning and memory in offspring. Imperatorin (IMP) is a naturally occurring furanocoumarin with many pharmacological properties. However, the effects of IMP on cognitive impairment induced by PS and the underlying molecular mechanisms remain unclear. We investigated the protective effect of IMP treatment after PS on learning and memory deficits in female offspring at postnatal 60 days. After treating prenatally-stressed offspring with IMP (15 and 30 mg/kg) for 28 days, we found that IMP increased body weight and ameliorated spatial learning and memory and working memory deficits in female offspring rats. Meanwhile, hippocampal Glu and serum corticosterone levels in prenatally-stressed offspring were significantly decreased after IMP administration. Additionally, IMP treatment significantly increased BDNF, TrkB, CaMKII, and CREB mRNA expression in the hippocampus of offspring rats. Furthermore, PS-mediated induction of RKIP protein and mRNA expression and glucocorticoid receptor protein expression in the hippocampus of offspring rats were significantly decreased by IMP treatment, and the protein expression of BDNF and TrkB and relative levels of p-EKR/ERK, p-CaMKIIα/CaMKIIα, and p-CREB/CREB were remarkably increased after IMP treatment. Taken together, IMP can ameliorate PS-induced learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling pathway and hypothalamic-pituitary-adrenal axis.

[Therapeutic effect of Jin Long capsule combined with neoadjuvant chemotherapy on invasive breast cancer and the expression change of multidrug resistance proteins].

Objective: To investigate the therapeutic effect of Jin Long Capsule (JLC) combined with neoadjuvant chemotherapy on the invasive breast cancer, and to explore the mechanism of JLC in inhibiting multidrug resistance of breast cancer. Methods: 200 patients were divided into experimental group and control group (100 cases per group). The control group used TEC regimen for neoadjuvant chemotherapy. And the experimental group was treated with TEC regimen combined with oral JLC. According to the Miller & Payne grading system (MP), the efficacy of neoadjuvant chemotherapy was evaluated based on histopathological changes of breast cancer after neoadjuvant chemotherapy. Adverse effect was evaluated according to the classification criteria of the National Cancer Institute of the United States-The Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The expression of P-glycoprotein (P-gp), glutathione thiol transferase (GST)-π and topoisomerase Ⅱα (TopoⅡα) in breast cancer tissues before and after neoadjuvant chemotherapy were detected by immunohistochemical staining. Results: There were 83 effective cases (83%) in the experimental group, which was higher than that in the control group (65.0%, P<0.05). The incidence of leukopenia, gastrointestinal reactions and alopecia in grade 3 to 4 of the experimental group were lower than those of the control group (all P<0.05). The positive rates of P-gp, GST-π and TopoⅡα expression in the control group were 65.0% (65/100), 61.0% (61/100) and 69.0% (69/100), respectively, and they were 80.6% (75/93), 78.5% (73/93) and 37.6% (35/93) after chemotherapy. The positive rates of P-gp and GST-π expression were significantly higher than those before chemotherapy (both P<0.05), whereas the positive rate of TopoⅡα expression was significantly lower than that before chemotherapy (P<0.05). In the experimental group, the positive rates of P-gp, GST-π and TopoⅡα expression before chemotherapy were 62.0% (62/100), 63.0% (63/100) and 69.0% (69/100), respectively, while after chemotherapy, they were 68.2% (60/88), 67.0% (59/88) and 63.6% (56/88). There was no significant difference in the positive rates and expression intensity of P-gp, GST-π and TopoⅡα before and after the chemotherapy (P>0.05). Conclusion: Jin Long Capsule (JLC) can inhibit multidrug resistance, improve the efficacy of neoadjuvant chemotherapy, and reduce adverse reactions of breast cancer.

Mutation screening of 10 cancer susceptibility genes in unselected breast cancer patients.

Variants of cancer susceptibility genes other than BRCA1/2 have been proved to be associated with increased risks of breast cancer. This study was performed to investigate the spectrum and prevalence of mutations in 10 cancer susceptibility genes in paired tumor/normal tissues of 292 unselected Chinese breast cancer patients. We performed an analysis of germline and somatic variants in ATM, CDH1, CHEK2, ESR1, GATA3, MAP3K1, MSH2, PALB2, RB1 and STK11 genes by integrating microfluidic PCR-based target enrichment and next-generation sequencing technologies. In total, 3 germline and 25 somatic deleterious mutations were found among 27 patients (9.25%), and 17 of them were novel mutations. Most deleterious mutations were prevalent in luminal A invasive breast cancer (P = .014). We also observed 83 variants of uncertain significance (VUS) in 100 patients (34.25%), 23 of which were predicted to be deleterious by in silico prediction programs (MetaSVM and MetaLR). VUS carriers had higher positive rate of lymph node metastasis than non-carriers (P = .008) and were predominantly present in ER+ tumors (P = .018). Our findings would enhance the understanding of the molecular mechanisms of breast cancer in Chinese population.

E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid.

Tumor cell extravasation is a multistep process preceded by cell rolling and arrest on the vessel wall via the formation of specific receptor-ligand bonds. The strength, availability, and number of receptor-ligand bonds regulate the rate by which tumor cells tether, roll, and adhere to vascular walls. Although the mechanics of selectin-mediated rolling have been extensively studied, little is known regarding how tumor cell rolling on selectins facilitates adhesion to a distinct substrate-bound protein with different kinetic properties. By using multicomponent protein patterning and a microfluidic system, we evaluated how E-selectin-dependent rolling modulates hyaluronic acid (HA) adhesion as a function of fluid shear, contact time, and the spacing between E-selectin and HA regions patterned on the substrate. We show that tumor cells rolling on E-selectin were ∼40-fold more likely to bind to HA than nonrolling cells in shear flow. Furthermore, E-selectin-dependent rolling promotes adhesion to HA by both physically slowing cells and enabling them to position proximal to the surface, thereby increasing the on rate of adhesion. A better understanding of tumor cell adhesion under physiologic shear would lead to the development of new diagnostic assays and pave the way to clinical approaches aimed ultimately to halt metastasis.-Shea, D. J., Li, Y. W., Stebe, K. J., Konstantopoulos, K. E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid.

Characteristics of fall-related traumatic brain injury in older adults.

BACKGROUND: Older adults admitted for falls and its complications, including traumatic brain injury (TBI), is increasing. Recent studies have shown that those with falls who presented to the emergency department (ED) had an increased frequency of ED revisits, especially those with head trauma. AIM: To determine the characteristics and predictors of fall-related traumatic brain injury (FRTBI) in older adults. METHODS: Retrospective medical chart review of 339 patients aged 65 years and older admitted for TBI in 2014 due to a fall. Characteristics analysed include demographics, fall circumstances, prior ED visits, polypharmacy, readmission, functional status and specialist outpatient clinic utilisation before and after FRTBI. RESULTS: A total of 339 (37.4%) patients admitted due to FRTBI was 65 years old and older; 112 (33.0%) for subdural haemorrhage (SDH); 227 (67.0%) for head injury (HI), with a mean age of 80 years. A total of 46 (41.1%) patients with SDH and 107 (47.1%) with HI had a previous ED visit within the last year, while 22 (19.6%) of SDH and 49 (21.6%) of HI had hospitalisation 3 months prior to FRTBI. FRTBI was associated with significant decline in activities of daily living, polypharmacy and increased specialist outpatient clinic appointments (P < 0.001). Mortality was 11 (3.2%). Mild cognitive impairment or dementia was significantly associated with admissions for FRTBI, 3.31 (95% confidence interval 1.68-6.51, P = 0.001) using adjusted logistic regression. CONCLUSION: FRTBI is associated with significant functional decline and increased resource utilisation with almost half of the patients having had prior ED visits or hospitalisation. Future studies should focus on falls risk assessment and interventions for high-risk older adults prior to discharge from ED and hospital, and its impact on readmissions due to FRTBI.

Prospective cohort study on the efficacy and safety of telbivudine used throughout pregnancy in blocking mother-to-child transmission of hepatitis B virus.

Women with chronic hepatitis B should maintain nucleotide analogue treatment to prevent disease progression during pregnancy. The aim of this study was to prospectively evaluate the efficacy and safety of telbivudine used throughout pregnancy for preventing hepatitis B virus (HBV) mother-to-child transmission (MTCT). From January 2012 to June 2014, women who were receiving telbivudine therapy and became pregnant were enrolled in group A at 28 weeks of gestation. Pregnant women with an HBV DNA level >106  IU/mL were enrolled in either group B (telbivudine started at 28 weeks of gestation) or group C (control group without treatment). MTCT was defined as infants who were positive for serum hepatitis B surface antigen at 7 months after birth. There were 41, 179 and 177 pregnant women (397 infants) enrolled in groups A, B and C, respectively. The HBV DNA load at 28 weeks of gestation and delivery was 1.50 ± 0.62 vs 1.45 ± 0.61, 8.05 ± 0.37 vs 4.24 ± 0.89 and 7.94 ± 0.62 vs 7.86 ± 0.73 log10 IU/mL in groups A, B and C, respectively. The rate of MTCT in group C was 4.60%, which was significantly higher than the rates in groups A and B (0% and 0.6%, respectively) (P = .043). The difference between group A and group B was not significant. The rates of neonatal congenital abnormalities were 2.4%, 0.6% and 2.3% in groups A, B and C, respectively, and there were no significant differences (P = .140). Telbivudine used throughout pregnancy may be safe and effective for mothers and infants, but it may not enhance the efficacy of an HBV MTCT block compared with treatment starting at 28 weeks of gestation (NCT02253485).

Lamivudine therapy during the second vs the third trimester for preventing transmission of chronic hepatitis B.

There are little data on the timing of initiating lamivudine therapy for preventing transmission of hepatitis B in highly viremic mothers. Between May 2008 and January 2015, we retrospectively enrolled mothers with HBV DNA >6 log10  copies/mL who received lamivudine during pregnancy, and we compared them to untreated mothers. The primary measurement was the vertical transmission rate. The secondary outcomes were the mothers' and infants' safety. Among 249 consecutive mothers enrolled, 66 and 94 received lamivudine during the second and third trimesters, respectively, and 89 were untreated. At delivery, maternal mean HBV DNA levels were significantly lower in mothers who received lamivudine (4.45 log10; vs 7.16 log10  copies/mL; P<.001). Lamivudine treatment was well tolerated. However, early treatment during the second trimester did not significantly increase the percentage of mothers achieving HBV DNA levels of <6 log10  copies/mL compared to those treated during the third trimester (98.5% vs 94.7%; P=.40). At the age of 28 weeks, the vertical transmission rates were significantly lower in the lamivudine-treated mothers vs in the untreated mothers (0% [0/160] vs 5.62% [5/89]; P<.001), but the rates were similar when comparing the two subgroups treated with lamivudine (0% [0/66] vs 0% [0/94], P>.05). The birth defect rates and mothers' and infants' adverse events were similar among the groups. Lamivudine treatment initiated in the second or third trimester for mothers with HBV DNA levels below 9 log10  copies/mL was equally safe and effective in preventing vertical transmission. Thus, lamivudine should be deferred until the third trimester to minimize foetal exposure and drug resistance.

[Decolorization of skin and hair-derived melanin by three ligninolytic enzymes].

Objective: To compare the decolorization efficiency of lignin peroxidase (LiP), manganese peroxidase (MnP) and laccase on eumelanin and pheomelanin, and to investigate the effect of topical administration of LiP solution on hyperpigmented guinea pigs skin induced by 308 nm excimer light. Methods: Pheomelanin-enriched specimens were prepared from human hair and cutaneous melanoma tissue using alkaline lysis method.Synthetic eumelanin was purchased from a commercial supplier.The same amount (0.02%) of melanin was incubated with the equal enzyme activity (0.2 U/ml) of ligninolytic enzymes for 3 h respectively.The absorbance at 475 nm (A(475)) in the enzyme-catalyzed solution was measured using ELISA microplate reader.The experimental hyperpigmentation model was established in the dorsal skin of brownish guinea pigs using 308 nm excimer light radiation.LiP and heat-inactivated LiP solution were topically applied at each site.Meanwhile, 3% hydroquinone and vehicle cream were used as control.The skin color (L value) was recorded using a CR-10 Minolta chromameter.Corneocytes were collected using adhesive taping method.The amount and distribution of melanin in the corneocytes and skin tissues was visualized by Fontana-Masson staining. Results: All three ligninolytic enzymes showed various degree of eumelanin and pheomelanin decolorization activity.The decolorization activity of LiP, MnP and laccase was 40%-70%, 22%-42% and 9%-21%, respectively.The similar lightening was shown in the skin treated with LiP solution and 3% hydroquinone.The amount of melanin granules in the corneocytes was 199±11 by LiP, which was less than that in untreated control (923±12) and heat-inactive control (989±13). The amount of melanin was decreased in the whole epidermis treated with hydroquinone, the epidermis thickness was increased as well. In contrast, melanin of LiP group was decreased only in the superficial epidermis, the epidermis thickness seemed to be normal. Conclusion: LiP exerts a potent decolorization activity for hair- or skin-derived pheomelanin as well as eumelanin.It remains to be further investigated whether LiP serves as a substitute for hydroquinone in skin lightening products.

The Influenza A Virus Non-structural Protein NS1 Upregulates The Expression of Collagen Triple Helix Repeat Containing 1 Protein.

Influenza A virus (IAV) infection induces a strong immune response and regulates the expression of many host proteins. The collagen triple helix repeat containing 1 (CTHRC1) protein is a secreted protein that exhibits increased expression during the viral infection process. However, the regulatory function of IAV on CTHRC1 expression is obscure. In this study, we investigated the effect of IAV on CTHRC1 expression and its regulatory mechanism. A total of 106 serum specimens from healthy people and 80 serum specimens from patients infected with IAV were collected. The CTHRC1 levels in the sera from the IVA patients and healthy individuals were measured using an enzyme-linked immunosorbent assay (ELISA), and the differences were statistically analysed. A549 cells were infected with the IAV or delNS1 virus. Additionally, A549 cells were cotransfected with a eukaryotic non-structural NS1 protein gene expression plasmid and the CTHRC1 gene promoter reporter plasmid (pCTHRC1-Luc), and, the luciferase activities were assessed. The CTHRC1 mRNA and protein expression were detected using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The serum CTHRC1 level was significantly higher in the IAV patients than in the healthy individuals. IAV upregulated the CTHRC1 mRNA and protein expression. The non-structural NS1 protein specifically activated CTHRC1 gene promoter activity and upregulated CTHRC1 mRNA and protein expression. The activation function had a dose-dependent effect, indicating that influenza virus upregulated CTHRC1 expression through its NS1 protein.