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:Farfarae Flos has the effect of cough suppression and phlegm elimination,with cough suppression as the main function.Studies have revealed that certain components of Farfarae Flos may be related to its cough suppressant effect,and some components have been confirmed to have cough suppressant activity.However,the antitussive material basis of Farfarae Flos has not been systematically elucidated.This study aims to elucidate the group of active ingredients in Farfarae Flos with cough suppressant activity by correlating the high performance liquid chromatography(HPLC)fingerprint of Farfarae Flos extract with its cough suppressant activity. Methods:HPLC was used to establish the fingerprint profiles of 10 batches of Farfarae Flos extract and obtain their chemical composition data.Guinea pigs were selected as experimental animals and the citric acid-induced cough model was used to evaluate the antitussive efficacy data of 10 batches of Farfarae Flos extract.SPF-grade healthy male Hartley guinea pigs were randomly divided into the S1 to S10 groups,a positive control group,and a blank control group(12 groups in total),with 10 guinea pigs in each group.The S1 to S10 groups were respectively administered Farfarae Flos extract S1 to S10(4 g/kg),the positive control group was administered pentoverine citrate(10 mg/kg),and the blank control group was administered purified water.Each group received continuous oral administration for 5 days.The guinea pigs were placed in 5 L closed wide-mouth bottles,and 17.5%citric acid was sprayed into the bottle with an ultrasonic atomizer at the maximum spray intensity for 0.5 minutes.The cough latency period and cough frequency in 5 minutes were recorded for each guinea pig.Grey relational analysis(GRA)and partial least squares regression(PLSR)were used to conduct spectral-effect correlation analysis of the chemical composition data of Farfarae Flos extract and the antitussive efficacy data,and predict the group of active ingredients in Farfarae Flos with antitussive activity.The bioequivalence verification was conducted to verify the predicted group of active ingredients in Farfarae Flos with antitussive activity:SPF-grade healthy male Hartley guinea pigs were randomly divided into a S9 group,an active ingredient group,a positive control group,and a blank control group(4 groups in total),with 10 guinea pigs in each group.The S9 group was administered Farfarae Flos extract S9(4 g/kg),the active ingredient group was administered the predicted combination of antitussive active ingredients(dose equivalent to 4 g/kg of Farfarae Flos extract S9),the positive control group was administered pentoverine citrate(10 mg/kg),and the blank control group was administered purified water.Each group received continuous oral administration for 5 days,and animal modeling and observation of efficacy indicators were the same as above. Results:The HPLC fingerprint of 10 batches of Farfarae Flos extract was established,and the peak area data of 14 main common peaks were obtained.The antitussive effect data of 10 batches of Farfarae Flos extract were obtained.Compared with the blank control group,the cough latence in the positive control group and S1,S2,S3,S4,S6,S7,S8,S9,S10 groups was prolonged(all P<0.01),while the cough frequency in 5 minutes in the positive control group and S1,S2,S4,S6,S8,S9,S10 groups was decreased(all P<0.05).The analysis of spectrum-effect relationship revealed that isochlorogenic acid C,isochlorogenic acid A,chlorogenic acid,isochlorogenic acid B,isoquercitrin,and rutin had high contribution to the antitussive effect of Farfarae Flos,and the 6 components were predicted to be the antitussive component group of Farfarae Flos.The verification of bioequivalence showed that there were no statistically significant differences in the antitussive effect between the S9 group and the antitussive component composition group(all P>0.05),which confirmed that isochlorogenic acid C,isochlorogenic acid A,chlorogenic acid,isochlorogenic acid B,isoquercetin,and rutin were the antitussive component group of Farfarae Flos. Conclusion:The analysis of spectrum-effect relationship combined with the verification of bioequivalence could be used to study the antitussive material basis of Farfarae Flos.The antitussive effect of Farfarae Flos is the result of the joint action of many components.

Gut microbiome is an important part of the human gut, which is closely related to human health and disease. Alzheimer's disease (AD) is a kind of neurodegenerative diseases, and its underlying pathogenesis has not been fully elucidated. In recent years, studies have shown obvious differences in gut microbiome composition between AD patients and healthy subjects. Comprehensive changes in gut microbiota composition may play a role in AD progression through the gut-brain axis. However, the mechanism of this interlinkage is not yet fully understood. In this review, we explore the mechanism of gut microbiota's influence in AD through gut-brain axis regulation.

Objective:To analyze the clinical characteristics and genetic variation of 2 children with developmental and epileptic encephalopathy 8 (DEE8).Methods:Whole-exome sequencing (WES) was performed to determine the potential variants in the probands. Candidate variants identified by WES were validated by Sanger sequencing and quantitative real-time polymerase chain reaction. X chromosome inactivation (XCI) detection was performed in the proband 1′s mother and proband 2 to detect the allelic expression difference of ARHGEF9. Results:Both of the cases showed global developmental delay. Proband 1 presented with delayed motor and speech development, intellectual disability, and seizures. Electroencephalography of proband 1 showed slow background activity, with spikes, spike and waves in bilateral frontal and midline regions during sleep. While proband 2 showed delay in acquisition of language, motor skills, and cognition, but no seizures. It was identified that proband 1 carried a novel maternally derived heterozygous splicing variant (c.925-2A>T) in ARHGEF9 by WES, which was verified in Sanger sequencing. The XCI in proband 1′s mother was observed, and the expression ratio of mutant ARHGEF9 and wild-type was 0∶100%. A novel exon 3-10 heterozygous deletion of ARHGEF9 was identified in proband 2, and this variant was not found in his unaffected parents. Conclusions:DEE8 disorders are relatively rare. Most of the patients have varying degrees of neurodevelopmental phenotype, but epilepsy is not a specific clinical manifestation. ARHGEF9 gene deletion and splicing variation may be the genetic cause of the 2 probands, and above findings have enriched the spectrum of variation and phenotype of DEE8.

Dyspepsia due to pancreatic exocrine insufficiency is a common complication after pancreatectomy； however， due to the lack of simple， efficient， and unified diagnostic methods， standardized treatment standards， and awareness of this disease among surgeons， it is difficult to get adequate diagnosis and treatment. Therefore， this article summarizes the research advances in the definition and pathogenesis of pancreatic exocrine insufficiency， the incidence rate of pancreatic exocrine insufficiency after different surgical procedures， and current diagnostic methods and treatment strategies， in order to provide a reference for further improving the diagnosis and treatment of pancreatic exocrine insufficiency after pancreatectomy.

Objective:To establish a model of improving diagnostic capability in infiltration depth of colorectal cancer (CRC) with combining narrow band imaging system(NBI) and endoscopic ultrasonography (EUS).Methods:CRC patients who were treated in Chongqing Fifth People′s Hospital from April 2015 to March 2021 were selected retrospectively as the research objects. All patients were diagnosed by postoperative pathological diagnosis. In the end, a total of 288 CRC patients were included. Using the random number table method, the study subjects were divided into modeling group ( n=192) and verification group ( n=96) at a ratio of 2∶1. The patients′ general information, NBI and EUS examination results were collected; logistic regression was used to analyze the independent risk factors of CRC submucosal infiltration, and a model was built to predict the depth of CRC infiltration; receiver operating characteristic (ROC) was used to identify the diagnostic ability of model. The diagnostic efficacy of CRC submucosal infiltration was verified internally by the verification group. Results:In the modeling group, lymph node metastasis ( OR=6.492, 95% CI: 5.128-7.855, P<0.001), low tumor differentiation ( OR=2.736, 95% CI: 1.731-3.741, P<0.001) and tumor length ( OR=2.049, 95% CI: 1.524-2.574, P<0.001) were independent risk factors for submucosal infiltration in CRC patients; The nomograph model constructed according to the above independent risk factors had a strong diagnostic ability for the depth of submucosal infiltration of CRC, and was internally validated in the validation group. AUC values of the modeling group and the validation group were 0.945 (0.935-0.955) and 0.951 (0.942-0.961), respectively. Conclusions:The nomogram model established by the combination of endoscopic narrow band imaging technology and ultrasound endoscopy can diagnose the depth of CRC infiltration better.

Basophils, which are considered as redundant relatives of mast cells and the rarest granulocytes in peripheral circulation, have been neglected by researchers in the past decades. Previous studies have revealed their vital roles in allergic diseases and parasitic infections. Intriguingly, recent studies even reported that basophils might be associated with cancer development, as activated basophils synthesize and release a variety of cytokines and chemokines in response to cancers. However, it is still subject to debate whether basophils function as tumor-protecting or tumor-promoting components; the answer may depend on the tumor biology and the microenvironment. Herein, we reviewed the role of basophils in cancers, and highlighted some potential and promising therapeutic strategies.

Objective: To investigate the feasibility and efficacy of transcatheter closure of anastomotic leakage after aortic surgery using Amplatzer Vascular Plug Ⅲ (AVP Ⅲ). Methods: A retrospective analysis was performed in 5 patients with anastomotic leakage after aortic surgery, who underwent transcatheter closure in our hospital from January to June 2017 using AVP Ⅲ. Surgeries were performed in 3 cases of Standford type A dissection, 1 case of ascending aortic aneurysm and 1 case of persistent truncus.There were 3 males,and age was (43.8±13.1) years old. Anastomotic leakages located at the ascending aorta in 4 patients, and the other one located between the aortic arch and the stent-graft.Three of them had aorta-right atrium fistula and patients suffered from progressive heart failure. False aneurysm between aorta and pulmonary artery was formed in 1 patient, and patent aortic false lumenwas found in the other patient. All the AVP Ⅲ were deployed based on a femoral arteriosus loop. Patients were followed up after transcatheter closure to observe the clinical results. Results: Six AVP Ⅲ were successfully implanted in the 5 patients. Trivial residual shunt was seen in 1 patient after closure. The patients were followed up 6 (1, 6) months. The cardiac function improved from NYHA class Ⅱ-Ⅳ to class Ⅰ-Ⅱ after the procedure in 3 congestive heart failure patients.The right atrium systolic pressure was significantly reduced after the procedure((8.7±1.8) mmHg (1 mmHg=0.133 kPa) vs. (24.3±2.3) mmHg, P=0.03). The diameter of the false aneurysm reduced in 1 patient after the procedure. Complete thrombosis formation of the thoracic false lumen was observed in 1 patient. Conclusion Transcatheter closure of anastomotic leakage after aortic surgery using AVP Ⅲ is feasible and effective according to our primary experience.