As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.Methods Male C57BL/6 mice were randomly divided into Sham group,cecal ligation puncture(CLP)-induced sepsis group,CLP with curcumin treatment(50,100,and 200 mg/kg)groups,and CLP with both curcumin(200 mg/kg)and TRX-1 inhibitor PX-12(25 mg/kg)treatment group.Inflammatory factors,MDA,MPO,and GSH levels in the lung tissue of the mice were detected.Beas-2B cells stimulated with lipopolysaccharide(LPS;1 μg/mL)were treated with 2.5,5,or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12,and the changes in MDA,Fe2+and ROS levels were assessed.Western blotting was performed to detect the protein expressions of TXNIP,TRX-1,GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells.Results The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6,IL-1β,TNF-α,MDA and MPO and decreased GSH expression.In Beas-2B cells,LPS stimulation significantly increased MDA and Fe2+levels and ROS release,increased TXNIP protein expression,and lowered the protein expression levels of TRX-1,GPX4 and X-CT,and these changes were also observed in the septic mice.Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells.Curcumin significantly decreased the release of inflammatory factors,MDA and MPO,increased GSH level,lowered Fe2+,MDA and ROS levels,increased TXNIP protein expression,and lowered the protein expressions of TRX-1,GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells.The protective effect of curcumin was effectively blocked by PX-12 treatment.Conclusion Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.

Objective To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.Methods Male C57BL/6 mice were randomly divided into Sham group,cecal ligation puncture(CLP)-induced sepsis group,CLP with curcumin treatment(50,100,and 200 mg/kg)groups,and CLP with both curcumin(200 mg/kg)and TRX-1 inhibitor PX-12(25 mg/kg)treatment group.Inflammatory factors,MDA,MPO,and GSH levels in the lung tissue of the mice were detected.Beas-2B cells stimulated with lipopolysaccharide(LPS;1 μg/mL)were treated with 2.5,5,or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12,and the changes in MDA,Fe2+and ROS levels were assessed.Western blotting was performed to detect the protein expressions of TXNIP,TRX-1,GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells.Results The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6,IL-1β,TNF-α,MDA and MPO and decreased GSH expression.In Beas-2B cells,LPS stimulation significantly increased MDA and Fe2+levels and ROS release,increased TXNIP protein expression,and lowered the protein expression levels of TRX-1,GPX4 and X-CT,and these changes were also observed in the septic mice.Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells.Curcumin significantly decreased the release of inflammatory factors,MDA and MPO,increased GSH level,lowered Fe2+,MDA and ROS levels,increased TXNIP protein expression,and lowered the protein expressions of TRX-1,GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells.The protective effect of curcumin was effectively blocked by PX-12 treatment.Conclusion Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.

Objective:To investigate the current nutrition support status of hospitalized small for gestational age infants born late preterm in hospitals of Beijing, and analyze the influencing factors.Methods:Clinical data of late preterm infants from 25 medical units in Beijing between October 2015 and October 2017 was collected and analyzed. Infants were assigned into two groups according to the relationship between their gestational age and birth body weight as small for gestational age(SGA) group and not small for gestational age(non-SGA) group, to compare their nutritional status and explore the related influential factors.Results:Totally, 1 347 late preterm infants were enrolled, including 730 males and 617 females, 151 in SGA group and 1 196 in non-SGA group. The data showed that the rate of exclusive breast-feeding was higher (5.3% vs 4.5%, P<0.01), and the increasing of milk volume was slower [11.0 vs 12.1 ml/(kg·d), P=0.003] in SGA group. More parenteral nutrition was used (77.5% vs 53.1%, P<0.01), and the duration of parenteral nutrition was longer (5.0 vs 2.0 days, P<0.01) in SGA group. The birth weight(1 940 vs 2 490 g, P<0.01), the lowest body weight(1 890 vs 2 400 g, P<0.01) and the discharged body weight(2 135 vs 2 530 g, P<0.01)were lower in SGA group. The SGA group showed lower body weight loss(3.1% vs 8.0%, P=0.015), slower weight growth(13.3 vs 33.0 g/d, P<0.01), and longer length of hospital stay (11.0 vs 8.0 days, P<0.01). In SGA group, the milk volume at discharge [145.6 vs 122.2 ml/(kg·d), P<0.01] and the caloric of enteral feeding at discharge [443.9 vs 384.1 kJ/(kg·d), P<0.01] were higher, the rate of infants who regained their birth weight during hospitalization(78.8% vs 57.9%, P<0.01) was higher, and the rate of ones who achieve full enteral feeding (31.8% vs 16.6%, P<0.01) was higher. A Cox regression analysis in which we set infants can achieve full enteral feeding as goal showed that independent factors associated with full enteral feeding at discharge in SGA group included the increasing of enteral feeding, the duration of parenteral nutrition, whether the length of hospital stay longer than 7 days or not whether exclusive breastfeeding and whether the mothers of enrolled infants were diagnosed gestational diabetes mellitus or placental abruption during pregnancy ( P<0.05). Conclusions:Infants in SGA group show slower increasing of milk volume and lower caloric amount of enteral feeding. More parenteral nutrition is used, and the duration of parenteral nutrition is longer in SGA group. Due to the longer length of hospital stay in SGA group, the milk volume and the caloric of enteral feeding at discharge are higher, more infants regain their birth weight during hospitalization, and more infants achieve full enteral feeding at discharge. Despite of higher portion of parenteral nutrition, infants in SGA group show slower weight growth and lower body weight at discharge.

Objective:To study the respiratory morbidity and the risk factors of respiratory complications in late-preterm infants.Methods:The data of 959 late-preterm infants in 21 hospitals in Beijing from October 2015 to April 2016 were collected.These infants were divided into the respiratory morbidity group (237 cases) and the control group (722 cases) according to whether they had short-term respiratory morbidity after birth.Clinical data of the two groups were compared.Results:Among the 959 late-preterm babies, 530 were male and 429 were female.Two hundred and thirty-seven cases (24.7%) developed short-term respiratory morbidity after birth.Infectious pneumonia developed in the most cases (81 cases, 8.4%), followed by transient tachypnea (65 cases, 6.8%), amniotic fluid aspiration (51 cases, 5.3%), and respiratory distress syndrome (24 cases, 2.5%) successively.All the infants recovered and discharged.There were no differences between gender and maternal age between 2 groups (all P>0.05). Compared with the control group, more late-preterm infants were delivered by cesarean section (73.4% vs.59.7%, χ2=14.43, P<0.001) and the 1-minute Apgar score was lower [(9.41±1.66) scores vs.(9.83±0.53) scores, t=5.40, P<0.001] in the respiratory morbidity group.The differences were statistically significant.There were more cases with maternal complications in the respiratory morbidity group that in the control group (66.7% vs.58.6%, χ2=4.877, P=0.027), but no difference in various complications between 2 groups was observed ( P>0.05). In the respiratory morbidity group, the most frequent complications were maternal hypertension and preeclampsia (27.8% vs.22.6%, χ2=2.728, P=0.099). There were no differences between 2 groups in gestational age, birth weight and birth length (all P>0.05). There were more infants small for gestational age and large for gestational age in the respiratory morbidity group than in the control group (18.8% vs.14.1%, 6.3% vs.2.4%, χ2=8.960, P=0.011). The duration of hospitalization of the respiratory morbidity group was significantly longer than that of the control group [(9.00±4.42) d vs.(6.82±4.19) d, t=6.676, P<0.001] since the infants with respiratory morbidity needed to be hospita-lized. Conclusions:Respiratory diseases occur in about 1/4 of late-preterm infants.Infants who are delivered by cesarean section and whose mothers are complicated with the maternal hypertension and preeclampsia should be monitored closely.Respiratory support should be provided for infants not appropriate for gestational age who are more likely to suffer from respiratory diseases, so that they can successfully pass through the transition period.

Objective:To investigate the status and influencing factors of enteral nutrition support in late preterm infants (34-36 +6 gestational weeks) treated in different grades of hospitals in Beijing. Methods:This was a prospective study involving late preterm infants treated in 25 hospitals in Beijing from October 2015 to October 2017. Data about nutritional management and nutrition-related complications were recorded. Exclusive breastfeeding status of the infants by gestational age(GA) and hospital levels was analyzed. The achievement of full enteral feeding and the potential influencing factors were also analyzed. t-test, Mann-Whitney U test, analysis of variance (ANOVA), Kruskal-Wallis test and Chi-square test were used for statistical analysis. Logistic regression and Cox regression analysis were used in multivariate analysis. Results:(1) A total of 1 463 late preterm infants with GA of 35.6±0.8 (ranging from 34.9 to 36.1) weeks was enrolled in this study. Compared with the infants with GA of 35-35 +6 and 36-36 +6 weeks, those born at 34-34 +6 gestational weeks had longer hospital stay [10 (8-13) vs 8 (7-10) and 7 (6-9) d, both P<0.05], greater loss of minimum weight [4.3% (2.6%-6.3%) vs 3.8% (2.0%-5.6%) and 3.3% (1.9%-5.5%), both P<0.05], higher incidence of apnea [5.3% (20/369) vs 2.1% (12/566) and 1.3% (7/528), both P<0.05] and respiratory distress syndrome (RDS) [7.1% (28/369) vs 3.0% (17/566) and 3.2% (17/528), both P<0.05], and lower percentage of failure to regain birth weight at discharge [32.5% (120/369) vs 38.7% (219/566) and 47.9% (253/528), both P<0.05]. Only the incidence of premature rupture of membranes among all maternal complications during pregnancy had statistical difference between 34-34 +6, 35-35 +6 and 36-36 +6 GA groups [6.2% (23/369) vs 12.7% (72/566) and 11.9% (63/528), χ2=10.244, P=0.007]. (2) The rate of enteral feeding increment in hospital was 13.7 (10.5-17.3) ml/(kg·d) and 46.0% (673/1 463) of the infants were fed formula. The exclusive breastfeeding rate increased from 4.5% (66/1 463) during hospitalization to 14.4% (211/1 463) at discharge. The breastfeeding rate at discharge varied widely among the 25 hospitals ( χ2=327.893, P<0.001) ranging from 32% to 0. (3) Logistic regression analysis demonstrated that gestational diabetes mellitus ( OR=2.426, 95% CI: 1.075-5.437, P=0.033) and premature rupture of membranes ( OR=8.726, 95% CI: 1.193-63.802, P=0.033) were the prenatal risk factors influencing the exclusive breastfeeding in late preterm infants. Enteral nutrition achieving 150 ml/(kg·d) and 120 kcal/(kg·d) (1 kcal=4.184 kJ) were noted for 28.4% (416/1 463) and 19.2% (281/1 463) of the late preterm infants at discharge, respectively. Cox regression analysis showed that hospital grades ( HR=1.470, 95% CI: 1.030-2.098, P=0.034), the length of hospital stay ( HR=1.162, 95% CI: 1.097-1.231, P<0.001), birth weight ( HR=0.946, 95% CI: 0.898-0.995, P=0.003), exclusive breastfeeding ( HR=2.354, 95% CI:1.031-5.374, P=0.042), feeding intolerance ( HR=3.677, 95% CI: 1.201-11.253, P=0.023), parenteral nutrition ( HR=1.900, 95% CI: 1.379-2.616, P<0.001), and the rate of enteral feeding advancement ( HR=1.426, 95% CI: 1.369-1.484, P<0.001) were independent factors associated with full enteral feeding at discharge. Conclusions:Exclusive breastfeeding rate in late preterm infants is low and enteral nutrition support varies greatly in different hospitals. The rate of enteral feeding increment is slow for hospitalized late preterm infants and most fail to achieve full enteral feeding at discharge. Gestational diabetes mellitus and premature rupture of membranes are prenatal risk factors affecting breastfeeding of late preterm infants. Those with low birth weight, exclusive breastfeeding in hospital, feeding intolerance, parenteral nutrition support, longer hospital stay or rapid enteral feeding advancement are more likely to achieve full enteral feeding at discharge.

PURPOSE: Chemoresistance is a concern in ovarian cancer patients, in whom survival remains. MicroRNA, a novel class of small RNAs, have frequently been found to be dysregulated in human malignancies and to act as negative regulators of gene expression. This study aimed to explore the function of miR-338-3p in cisplatin resistance in ovarian cancer and potential molecular mechanisms thereof. MATERIALS AND METHODS: The expression levels of miR-338-3p and WNT2B in ovarian cancer tissues and cells were estimated by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell, and flow cytometry assays were used to assess biological role of miR-338-3p in vitro. Western blot assay was conducted to measure protein expression of WNT2B, epithelial-mesenchymal transition (EMT)-related proteins, and apoptosis-related proteins. The relationship between miR-338-3p and WNT2B was confirmed by dual-luciferase reporter. Finally, a xenograft tumor model was developed to explore the effects of overexpression of miR-338-3p on tumor growth in ovarian cancer in vivo. RESULTS: MiR-338-3p was downregulated in cisplatin resistant ovarian cancer tissues and cells. Mechanistically, high expression of miR-338-3p enhanced cell sensitivity to cisplatin by inhibiting proliferation, motility, and EMT and by promoting apoptosis via targeting WNT2B expression in vitro. Furthermore, overexpression of miR-338-3p increased cisplatin sensitivity among ovarian cancer in an in vivo xenograft tumor model. CONCLUSION: MiR-338-3p enhances the sensitivity of ovarian cancer cells to cisplatin by downregulating WNT2B.
Apoptosis ; Blotting, Western ; Cisplatin ; Epithelial-Mesenchymal Transition ; Flow Cytometry ; Gene Expression ; Heterografts ; Humans ; In Vitro Techniques ; MicroRNAs ; Ovarian Neoplasms ; Polymerase Chain Reaction ; RNA

Objective To investigate the risk factors of hyperbilirubinemia in late preterm infants. Methods The clinical data of 815 late preterm infants (449 males and 366 females) from 25 hospitals in Beijing were collected from October 2015 to April 2016, including 340 cases(41.7％) with hyperbilirubinemia (hyperbilirubinemia group), and 475 cases without hyperbilirubinemia (control group). The clinical data of two groups were compared, and the maternal factors influencing hyperbilirubinemia in late preterm infants were analyzed with logistic regression. Results There were no significant differences in gender ratio (M:F 1.39 vs. 1.12, t=1.811,P=0.172)and birth weight[(2502.6±439.6)g vs. (2470.2±402.9)g,χ2=2.330,P=0.127)]between two groups. The incidence rates of hyperbilirubinemia in infants of 34 wks, 35 wks and 36 wks of gestational age were 22.9％(87/174), 35％(119/300) and 42.1％(143/341) respectively (χ2=1.218,P=0.544). The multivariate logistic regression analysis indicated that the maternal age(OR=1.044,95％ CI:1.010-1.080,P=0.011)was independent risk factor and multiple births(OR=1.365,95％CI:0.989-1.883,P=0.048), premature rupture of membranes(OR=2.350,95％ CI:1.440-3.833,P=0.001), cesarean section(OR=1.540,95％CI:0.588-4.031,P=0.014)were risk factors for hyperbilirubinemia in late preterm infants. Conclusions The incidence of hyperbilirubinemia in late preterm infants is relatively high. Maternal age, multiple births, premature rupture of membranes and cesarean section are risk maternal factors related to hyperbilirubinemia in late preterm infants.