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 establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

OBJECTIVE: To investigate the persistent damage of learning and memory ability after the cessation of sub-chronic manganese(Mn)-exposure in rats. METHODS: Specific pathogen free weaning male SD rats were randomly divided into control group and low-, medium-and high-dose groups based on body weight, with 6 rats in each group. Rats were intraperitoneally injected with Mn chloride(MnCl_2·4 H_2O) at the concentrations of 0, 5, 10, or 20 mg/kg body weight, 5 days per week for 6 weeks and continued to be observed for 12 weeks after the cessation of Mn-exposure. During the experiment, the body mass of the rats was weighed. Learning and memory ability was evaluated by a Morris water-maze task at the 6 th weeks of Mn-exposure(cessation of Mn-exposure of week 0), the 6 th and 12 th week of the cessation of Mn-exposure. The organ coefficients of heart, liver, spleen, kidney and testicles were evaluated after the cessation of Mn-exposure on week 12. RESULTS: The body mass of the high-dose group was lower than that of the other 3 groups(P<0.05) at the 4 th and 6 th week of Mn-exposure and the 2 nd week of the cessation of Mn-exposure. There was no significant difference in body mass between the groups(P>0.05) on the 12 th week of the cessation of Mn-exposure. The escape latency of high-dose group was higher than that of the control group(P<0.05), and the number of platform crossings in the low-, medium-and high-dose groups were fewer than that in the control group(P<0.05) after the cessation of Mn-exposure. The escape latency was shorter and the numbers of platform crossings were higher on the 6 th and 12 th week of the cessation of Mn-exposure(P<0.05) when compared with that of the 6 th week of Mn-exposure rats. There was no statistical significance in the organ coefficients of heart, liver, spleen, kidney and testicles among the 4 groups at the 12 th week of the cessation of Mn-exposure in rats(P>0.05).CONCLUSION: Sub-chronic Mn exposure can impair learning and memory ability of rats, and the damage persists after the cessation of Mn-exposure.

Cryptococcal meningitis is a common and refractory central nervous system infection,with high rates of mortality and disability.The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion.Based on the current situation of cryptococcal meningitis in China,the management of cryptococcal meningitis includes 6 aspects:introduction,microorganism identification,clinical manifestations and diagnosis,principles of antifungal therapy,treatment of refractory and recurrent meningitis,treatment of intracranial hypertension.There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis.This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines.The importance of early diagnosis,combined long-term antifungal therapy,control of intracranial hypertension are emphasized.

Objective To study the effects of hyperbaric oxygen ( HBO ) preconditioning on the expression of heme oxygenase-1 ( HO-1 ) and anaplastic lymphoma kinase ( ALK ) in cerebral ischemia-reperfusion ( IR) rats.Methods The Sprague-Dawley male rats were randomly divided into 3 groups: the middle cerebral artery occlusion (MCAO) and reperfusion group (n=8), the sham surgical group (n=7) and the HBO preconditioning +MCAO and reperfusion group (n=8).The HBO preconditioning rats were exposed to hyperbaric environment at a pressure of 0.2 MPa with 85％ oxygen concentration , 1 hour a day, for a succession of 7 days.Modified Longa method was used to develop middle cerebral artery occlusion ( MCAO) model and reperfusion was performed 2 hours after ischemia .Twenty-fours after termination of reperfusion , the samples were collected to perform TTC staining , and RT-PCR was used to detect the expression levels of HO-1 and ALK.Results HBO preconditioning could significantly reduce the scope of cerebral infarction ( P <0.01).Additionally, the expression levels of HO-1 and ALK in the ischemia and reperfusion group were markedly increased , as compared with those of the sham surgical group , while the expression levels of HO-1 and ALK in the HBO group were considerably decreased , however , the expression level of HO-1 was obviously increased as compared with that of the sham surgical group (P<0.05).Conclusion HBO preconditioning could significantly decrease the down-regulation of HO-1 and ALK in the brain tissue of ischemia and reperfusion rats , which indicated that it might have a protective effect on the brain damage induced by ischemia and reperfusion .

Objective To study the effects of hyperbaric oxygen ( HBO ) preconditioning on the expression of heme oxygenase-1 ( HO-1 ) and anaplastic lymphoma kinase ( ALK ) in cerebral ischemia-reperfusion ( IR) rats.Methods The Sprague-Dawley male rats were randomly divided into 3 groups: the middle cerebral artery occlusion (MCAO) and reperfusion group (n=8), the sham surgical group (n=7) and the HBO preconditioning +MCAO and reperfusion group (n=8).The HBO preconditioning rats were exposed to hyperbaric environment at a pressure of 0.2 MPa with 85％ oxygen concentration , 1 hour a day, for a succession of 7 days.Modified Longa method was used to develop middle cerebral artery occlusion ( MCAO) model and reperfusion was performed 2 hours after ischemia .Twenty-fours after termination of reperfusion , the samples were collected to perform TTC staining , and RT-PCR was used to detect the expression levels of HO-1 and ALK.Results HBO preconditioning could significantly reduce the scope of cerebral infarction ( P <0.01).Additionally, the expression levels of HO-1 and ALK in the ischemia and reperfusion group were markedly increased , as compared with those of the sham surgical group , while the expression levels of HO-1 and ALK in the HBO group were considerably decreased , however , the expression level of HO-1 was obviously increased as compared with that of the sham surgical group (P<0.05).Conclusion HBO preconditioning could significantly decrease the down-regulation of HO-1 and ALK in the brain tissue of ischemia and reperfusion rats , which indicated that it might have a protective effect on the brain damage induced by ischemia and reperfusion .

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.