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.

Purpose: This study aimed to identify the altered pathways and genes associated with freezing damage in human sperm during cryopreservation by multiomics analysis. Materials and Methods: Fifteen fresh human semen samples were collected for transcriptomic analysis, and another 5 fresh human semen samples were obtained for metabolomic analysis. For each semen sample, 1 mL was cryopreserved, and another 1 mL was left untreated for paired design. The results were then combined with previously published proteomic results to identify key genes/pathways. Results: Cryopreservation significantly reduced sperm motility and mitochondrial structure. Transcriptomic analysis revealed altered mitochondrial function, including changes in tRNA-methyltransferase activity and adenosine tri-phosphate/adenosine di-phosphate transmembrane transporter activity. Metabolomic analysis showed that the citrate cycle in mitochondria was significantly altered. Combining transcriptomic, proteomic, and metabolomic analyses revealed 346 genes that were altered in at least two omics analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that metabolic pathways were significantly altered and strongly associated with mitochondria. Five genes were altered in all three omics analyses: COL11A1, COL18A1, LPCAT3, NME1, and NNT. Conclusions Five genes were identified by multiomics analysis in human cryopreserved sperm. These genes might have specific functions in cryopreservation. Explorations of the functions of these genes will be helpful for sperm cryopreservation and sperm motility improvement or even for reproduction in the future.

Objective:To evaluate the role of brain-derived neurotrophic factor-antisense long-chain non-coding RNA (BDNF-AS) in amygdala in the development of neuropathic pain (NP) in rats.Methods:Healthy clean-grade male Sprague-Dawley rats, aged 2 months, weighing 200-260 g, were used to develop NP model via ligation of left L 5-6 spinal nerve, while control group was only subjected to the exposure of L 5-6 spinal nerve without ligation.This study was performed in two parts.Experiment Ⅰ Fifty-six rats were divided into 3 groups by the random number table method: sham operation group (Sham group, n=8), NP group ( n=24) and BDNF ( n=24). In BDNF group, exogenous BDNF was injected into bilateral amygdala at 1, 3, 6, 13 and 20 days after development of the model, with 100 pmol at each side.Eight rats were sacrificed at 7, 14 and 21 days after the model was developed in NP and BDNF groups and after the model was developed in Sham group, the brains were removed, and the amygdala was isolated for determination of the BDNF content (by enzyme-linked immunosorbent assay), the number of BDNF-positive cells (by immunohistochemistry), and expression of BDNF-AS (by real-time quantitative polymerase chain reaction). Experiment Ⅱ Thirty-two rats were divided into 4 groups ( n=8 each) using the random number table method: Sham operation group, NP group, BDNF group and siRNA group.At 1, 3, 6, 13 and 20 days after development of the model, exogenous BDNF 100 pmol and siRNA-BDNF-AS 50 nmol were injected into the amygdala at each side in BDNF group and siRNA group, respectively.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before development of the model (T 0) and at 4, 7, 14 and 21 days after development of the model (T 1-4). After the last behavioral test was completed, the rats were sacrificed, and the spinal cord tissues were collected to measure the contents of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α). Results:Experiment Ⅰ Compared with Sham group, the content of BDNF and the number of BDNF positive cells were significantly decreased, and the expression of BDNF-AS was up-regulated at each time point after development of the model in group NP ( P<0.05). Compared with NP group, the content of BDNF and the number of BDNF positive cells were significantly increased, and the expression of BDNF-AS was down-regulated at each time point after development of the model in group NP ( P<0.05). Experiment Ⅱ Compared with Sham group, MWT was significantly decreased and TWL was shortened at T 1-4, and the contents of IL-1β, IL-6 and TNF-α were increased in NP, BDNF and siRNA groups ( P<0.05). Compared with NP group, MWT was significantly increased and TWL was prolonged at T 1-4, and the contents of IL-1β, IL-6 and TNF-α were decreased in BDNF and siRNA groups ( P<0.05). Conclusions:The mechanism underlying the development of NP may be related to the up-regulation of BDNF-AS expression in amygdala, inhibition of BDNF synthesis and promotion of inflammatory responses in the spinal cord of rats.

Objective:To investigate the levels of periphreal blood free carnitine and amino acids in healthy pregnant women in the third trimester and their association with maternal, fetal, and neonatal cardiac function and structure.Methods:This prospective descriptive study included healthy singleton pregnancies who underwent routine obstetric examination and delivered in two district maternal and child health hospitals (one in the urban and one in the suburb an area) in Beijing from June 2017 to February 2018. All recruiters had serology Down's syndrome screening test at (18±1) gestational weeks. Besides measurement of amino acids and free carnitine levels in whole blood and urine samples by liquid chromatography-tandem mass spectrometry, all cases underwent maternal and fetal echocardiography at (35±1) weeks of gestation. And neonatal echocardiography was performed after delivery to assess the heart function and structure. Antenatal factors were also collected, including maternal education background, age at first marriage and conception, gravidity, and folic acid supplement in early pregnancy. Statistical analysis was performed using t-test, ANOVA, Chi-square test, Pearson correlation coefficient, and Kappa test. Results:A total of 493 mother-neonate dyads were enrolled in this study. Blood free carnitine levels in the healthy pregnant women in the third trimester ranged from 5.09 to 59.17 μmol/L (reference value: 10.00-50.00 μmol/L) with an average value of (13.03±3.87) μmol/L. None was found with structural abnormalities by cardiac ultrasound, showing an average left ventricular end diastolic diameter (LVEDD) and end systolic diameter (LVESD) of (45.70±3.08) mm and (29.17±3.12) mm, respectively, and left ventricular ejection fraction (LVEF) of all cases were over 55%. No cardiac malformation was detected by the third-trimester fetal echocardiography. The average birth weight of the 493 newborns was (3 340±313) g. Those whose birth weight <2 500 g and >4 000 g were accounted for 1.0% (5 cases) and 3.0% (15 cases) with the average maternal blood free carnitine level of (13.25±2.17) μmol/L (10.46-19.21 μmol/L) and (12.64±2.50) μmol/L (8.78-17.73 μmol/L) ( t=0.42, P>0.05). The average LVEDD and LVESD of the 493 newborns were (17.21±1.27) mm and (11.03±1.30) mm, respectively. For the 64 newborns (13.0%) whose LVEF<60%, the maternal blood free carnitine level was (12.93±2.78) μmol/L (7.34-22.13 μmol/L), showing no statistical difference ( t=-0.29, P>0.05) with those 59 neonates (12.0%) whose LVEF over 75% and maternal carnitine level of (13.09±3.24) μmol/L (8.66-27.49 μmol/L). All cases were divided into four groups based on the quartiles of maternal blood free carnitine level and no significant difference in maternal or neonatal LVEDD or LVEF was observed among these groups (all P>0.05). Conclusions:Blood free carnitine concentration in healthy pregnant women in the third trimester is at the lower limit of normal range, and no significant effect on maternal cardiac function and fetal cardiac structure is seen. However, the effect of low maternal carnitine level in the third trimester on children's myocardial function and whether carnitine should be supplemented in the third trimester are worthy of further investigation with larger sample size.

Objective:To investigate the clinical value of peripheral monocyte and neutrophil count in predicting the response of patients with metastatic non-small cell lung cancer (mNSCLC) to immunosuppressive checkpoint inhibitors (ICI).Methods:The clinical data of 34 adult mNSCLC patients who received nafulizumab or pabolizumab in Danzhou People's Hospital of Hainan Province from January 2017 to March 2019 were retrospectively analyzed. The correlation of the demographic characteristics, clinical data, hematological examination results in the first two weeks before the treatment and two weeks after ICI treatment with prognosis was recorded and observed.Results:The baseline mean monocyte count [(0.52±0.09)×10 9/L vs. (0.60±0.12)×10 9/L] and neutrophil count [(4.27±0.87)×10 9/L vs.(5.39±1.02)×10 9/L] of patients with ICI reaction were lower than those of patients without ICI reaction, and the differences were statistically different ( t = -2.572, -2.727, all P < 0.05). However, there was a negative correlation between the monocyte count of the patients who responded to ICI and the reaction time ( r = -0.507, P < 0.05). The median reaction time in patients with monocyte count >0.70×10 9/L was shorter than that in patients with monocyte count ≤0.70×10 9/L (8 weeks vs. 12 weeks, χ2=4.162, P = 0.041). There was no correlation between monocyte count and time of reaction duration, progression of free survival (PFS) and overall survival (OS) ( r = -0.214, 0.182, 0.232, all P > 0.05). The decrease rate of neutrophil count in response group was higher than that in non-response group (22% vs. 2%, P < 0.05). After the first administration, cutoff value of neutrophil count was 4.2×10 9/L; the response rate of patients with neutrophil count ≤ 4.2×10 9/L was higher than that of patients with neutrophil count > 4.2×10 9/L [86.7% (13/15) vs. 36.8% (7/19), χ2=6.657, P < 0.05]. Conclusion:Peripheral blood monocyte and neutrophil count can predict the response to ICI therapy in patients with mNSCLC.

[Abstract] Objective: To investigate the effect of sphingosine kinase 1 (SphK1) knockdown on the proliferation and migration of colon cancer RKO cells induced by mesenchymal stem cells (MSCs). Methods: RKO cells were treated with MSCs conditioned medium (MSC-CM) or control medium (Control-CM), respectively. Cell proliferation was detected by CCK-8 assay. Cell migration ability was tested by Transwell chamber assay. The proteins expression of Ki-67, MMP-2/9, CD44 and CD133 was detected by Western blotting. Then, the expression of SphK1 in RKO cells was suppressed by targeted gene lentivirus shRNA vector transfection. The effects of SphK1 knockdown on the proliferation, migration and protein expressions of Ki-67, MMP-2/9, CD44 and CD133 of RKO cells induced by MSC-CM were observed. Results: The RKO cells proliferation was promoted by MSC-CM in a time-dependent manner; moreover (P<0.05), the migration ability of cells was significantly enhanced after being treated with MSC-CM(P<0.01). In addition, MSC-CM significantly increased the protein expressions of Ki-67, MMP-2/9, CD44 and CD133(all P<0.05 or P<0.01). Lentiviral ShRNA vector transfection could significantly inhibit the expression of SphK1. Down-regulation of SphK1 significantly inhibited the proliferation, migration and protein expressions of Ki-67, MMP-2/9, CD44 and CD133 of RKO cells induced by MSC-CM(all P<0.05 or P<0.01). Conclusion: MSC-CM promotes the proliferation and migration of colon cancer RKO cells. Down-regulation of SphK1 reverses the cell proliferation and migration induced by MSC-CM via inhibiting the expression of MMP-2/9, CD44 and CD133.

Objective To explore the clinical characteristics and risk factors of strokeassociated pneumonia (SAP) in patients with acute cerebral hemorrhage.Methods A total of 375 patients with acute cerebral hemorrhage were selected from the department of neurology and neurosurgery during January 2013 to December 2015 in our hospital.According to the incidence of SAP,they were divided into the observation group (complicated with SAP,n =79) and control group (not complicated with SAP,n =296).Clinical data were collected,and clinical characteristics and related risk factors of SAP complicated with acute cerebral hemorrhage were analyzed.Results Among all the 79 SAP patients in observation group,there were 38 cases with gram-negative bacterial infections,25 cases with gram-positive bacterial infections,16 cases with mixed infections.The SAP incidence in patients with massive hemorrhage was higher than that in patients with nonmasive hemorrhage (x2 =11.301,P＜ 0.01),and was higher in patients with cerebellum,brainstem,ventricle,thalamus and multifoeal hemorrhage than that in patients with basal ganglion and brain lobe hemorrhage(x2 =4.023,P＜0.05).The hospitalization days of the observation group was longer than that of the control group [(32.7 ± 16.2) versus (17.3 ± 6.7),t=2.93,P＜ 0.01].The mortality of the observation group was higher than that of the control group (24.1％ versus 3.7％),(x2 =8.720,P＜ 0.01).Multivariate Logistic regression analysis showed that age≥ 65 (OR =4.87),underlying lung diseases (OR =5.30),bulbar paralysis (OR =7.39),disorder of consciousness (OR=4.11),NIHSS score ＞ 4 (OR =3.96),invasive airway operations (OR=3.78),gastric tube (OR =4.37),H2-receptor blocking agents application (OR =2.09) were independent risk factors for SAP in acute intraerebral hemorrhage patients.Conclusions Gram-negative bacteria are the main pathogens of SAP in patients with acute cerebral hemorrhage.The patients complicated with SAP after acute cerebral hemorrhage have poor prognosis including prolonged hospitalization period and higher mortality.SAP in acute intraerebral hemorrhage patients is closely related to the following factors:age≥65,underlying lung diseases,bulbar paralysis,disorder of consciousness,NIHSS score ＞ 4,invasive airway operations,gastric tube,H2-receptor blocking agents.

OBJECTIVETo investigate the epidemiological status of cholestasis in first-hospitalized patients with chronic liver disease in Shanghai, and to provide a scientific basis for developing prevention and treatment measures.

METHODSFrom April 2005 to September 2014, 5,146 first-hospitalized patients in Shanghai with a diagnosis of chronic liver disease were enrolled in this study. Clinical data of the 4,660 patients who fit the study criteria for participation were collected for retrospective analysis.Diagnosis of cholestasis was made according to serum alkaline phosphatase (ALP) levels higher than 1.5 times the upper limit normal (ULN) and gamma-glutamyltransferase (GGT) levels higher than 3 times the ULN. The incidence rate of cholestasis was assessed for relation to age, sex, etiology, and type of liver disease, and statistically compared to the general clinical data and specific biochemical indicators with potential sex-related differences. T-test and chi-square test were performed for the statistical analyses.

RESULTSOf the 4,660 study participants, 10.26% had cholestasis; the prevalence of cholestasis increased with increasing age in male patients. The distribution of the cholestasis incidence according to the type of chronic liver disease was: 75.00%, primary sclerosing cholangitis; 42.86%, primary biliary cirrhosis; 35.97%, hepatic tumor; 30.77%, autoimmune hepatitis; 28.31%, drug-induced liver disease; 16.46%, alcoholic hepatitis; 13.98%, cryptogenic cirrhosis; 12.99%, schistosomal cirrhosis; 7.53%, alcoholic cirrhosis; 7.32%, mixed cirrhosis; 5.94%, viral liver cirrhosis; 2.70%, nonalcoholic fatty liver disease. There was no significant difference in the prevalence of cholestasis between the two sexes. In the patients with cholestasis, the levels of GGT and total bilirubin were significantly different between the two sexes.

CONCLUSIONThe incidence rate of cholestasis in first-hospitalized patients with chronic liver disease was 10.26%, and the rate increased with increased age. Patients with primary sclerosing cholangitis or primary biliary cirrhosis had higher incidence rates of cholestasis. Incidence rates of cholestasis of the various chronic liver diseases were not related to sex.

Bilirubin ; China ; Cholestasis ; Chronic Disease ; Humans ; Incidence ; Liver Diseases ; Male ; Prevalence ; Retrospective Studies ; gamma-Glutamyltransferase