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.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective To analyze the effect of neurofeedback training based on early start Denver model(ESDM)on children with autism spectrum disorder(ASD). Methods From August,2020 to May,2024,a total of 60 children with ASD from Hangzhou Children's Hospital were randomly divided into control group(n=30)and observation group(n=30).The control group received ESDM intervention,while the observation group received neurofeedback training in addition,for six months.They were assessed with Autism Treatment Evaluation Checklist(ATEC)and Psycho-Educational Profile-3rd Edition(PEP-3). Results After treatment,the score of ATEC was lower in the observation group than in the control group(t=3.545,P<0.05),the scores of cognition(t=2.236,P=0.029),emotional expression(t=2.293,P=0.025)and problem be-havior(Z=2.099,P=0.036)were higher in the observation group than in the control group.The score differenc-es of ATEC(Z=3.620,P<0.001),and cognition(Z=2.920,P<0.05)and problem behaviors(Z=4.209,P<0.05)of PEP-3 before and after intervention were higher in the observation group than in the control group. Conclusion Combination of neurofeedback training could improve the effect of ESDM on ASD.

Objective:To compare the curative effects between modified double-reverse traction technique and traditional open reduction in the treatment of tibial plateau fractures.Methods:A retrospective study was conducted to analyze the data of 70 patients with Schatzker type Ⅳ-Ⅴ tibial plateau fracture who had undergone surgical treatment at The Third Department of Orthopaedics, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine from January 2017 to December 2022. The patients were divided into an observation group treated with modified double-reverse traction and a control group treated with traditional open reduction. In the observation group of 37 cases, there were 20 males and 17 females with an age of (44.6±13.5) years, and 9 cases of type Ⅳ and 28 cases of type V by the Schatzker classification; in the control group of 33 cases, there were 18 males and 15 females with an age of (45.9±13.7) years, and 10 cases of type Ⅳ and 23 cases of type Ⅴ by the Schatzker classification. The 2 groups were compared in terms of operation time, length of main incision, intraoperative blood loss, Rasmussen imaging score before discharge, and knee function score of American Hospital for Special Surgery (HSS), Visual Analogue Scale (VAS), fracture healing and complications at 6 months postoperatively.Results:There was no significant difference in the preoperative general data between the 2 groups, showing group comparability ( P>0.05). All patients were followed up for (14.3±1.4) months. The observation group was significantly better than the control group in operation time [(113.9±11.4) min versus (151.82±10.37) min], length of main incision [4 (4, 5) cm versus 6 (6, 7) cm], intraoperative blood loss [30 (20, 35) mL versus 55 (50, 65) mL], VAS [0 (0, 0) point versus 0 (0, 1) points] and HSS score [(89.8±3.1) points versus (86.0±3.5) points] ( P<0.05). There were no significant differences between the 2 groups in Rasmussen imaging score before discharge, or fracture healing rate or complication rate at 6 months postoperatively ( P>0.05). Conclusion:In the treatment of Schatzker type Ⅳ-Ⅴ tibial plateau fractures, modified double-reverse traction technique is worthy of clinical application and promotion, because it is advantageous over traditional open reduction in terms of shorter operation time, smaller surgical incision, less intraoperative blood loss, less postoperative pain and better knee function.

Objective:To explore the regulatory role of the melanin-concentrating hormone (MCH) neural pathway from the lateral hypothalamus (LHA) to the nucleus accumbens (NAc) in modulating anxiety-like behavior in mice.Methods:Totally 37 male SPF-grade C57BL/6J mice, aged 6 to 8 weeks and weighed 18-22 g, were used for the following experiment: (1) Five mice received an injection of Fluoro-Gold (FG) into the NAc, followed by retrograde tracing combined with immunofluorescence staining after one week to observe the coexistence of FG and MCH immunopositive neurons in the LHA.(2)Thirty-two mice were injected with adeno-associated virus which could activate the MCH neurons into the LHA.After two weeks, they were randomly divided into four groups and received different drug injections: normal saline (NS, intraperitoneal injection)+ NS (1.5 μL, injection in the NAc) group, NS(intraperitoned injection) + SNAP94847 (SNAP, 2 mg/mL, 1.5 μL, injection in the NAc) group, chlorprothixene N-oxide (CNO, 0.15 mg/kg, intraperitoned injection) + NS(1.5 μL, injection in the NAc) group, and CNO(intraperitoned injection) + SNAP(1.5 μL injection in the NAc) group, and the SNAP94847 was an antagonist for MCH typel receptor.The open field test (OFT), elevated plus maze (EPM), and marble burial test (MBT) were employed to assess the impact of chemogenetic activation of MCH neurons on anxiety-related behavior in mice.Results:(1) The results of FG retrograde tracing combined with immunofluorescence histochemistry showed that MCH neurons in the LHA project their neural fibers to NAc neurons.(2) In the chemogenetic experiment, there was no significant interaction effect between CNO and SNAP in terms of the duration of stay ( Finteraction=2.899, P>0.05) and the distance moved ( Finteraction=1.603, P>0.05) in the central area during OFT experiments.However, the main effects of both CNO and SNAP intervention were significant in the duration of stay ( FCNO=6.767, FSNAP=7.656, both P<0.05) and the distance moved ( FCNO=12.480, FSNAP=7.999, both P<0.01) in the central area.Compared to the NS+ NS group, mice in the CNO+ NS group exhibited a shortened duration of stay ((89.00±19.16)s, (63.75±13.58)s, P<0.05) and a decrease in distance moved ((593.79±108.18)cm, (426.81±66.14)cm, P<0.05) in the central area.In contrast, mice in the CNO+ SNAP group had an extended duration of stay ((87.38±16.57)s) and an increase in distance moved ((569.27±73.20)cm) in the central area compared to the CNO+ NS group.There was no significant interaction effect between CNO and SNAP in the number of entries ( Finteraction=2.79, P>0.05) and the dwell time ( Finteraction=2.871, P>0.05) into the open arms of EPM experiments.However, the main effects of both CNO and SNAP interventions in the number of entries ( FCNO=10.43, P<0.01; FSNAP=4.96, P<0.05) and the dwell time ( FCNO=5.232, FSNAP=7.597, both P<0.05) into the open arms were significant.Compared to the NS+ NS group, mice in the CNO+ NS group showed a decrease in the number of entries ((13.13±3.36), (7.63±3.70), P<0.01) and a decrease in open arm dwell time ((37.68±11.37) s, (22.98±7.00) s, P<0.05) into the open arms.The CNO+ SNAP group had an increased number of entries (12.00±3.02) and an increased dwell time ((39.41±10.58)s) into the open arms compared to the CNO+ NS group(both P<0.05).There was no significant interaction effect between CNO and SNAP in the MBT experiment ( Finteraction=2.746, P>0.05).However, the main effects of both CNO and SNAP interventions were significant ( FCNO=8.125, P<0.01; FSNAP=5.383, P<0.05).Compared to the NS+ NS group, the number of buried beads increased in the CNO+ NS group ((16.13±2.10), (11.88±3.23), P<0.05).Conversely, the number of buried beads decreased in the CNO+ SNAP group compared to the CNO+ NS group ((12.38±2.33), (16.13±2.10), P<0.05). Conclusion:Enhanced activity in the MCHergic neural pathway from LHA to NAc can promote anxiety-like behavior in mice, providing new insights into the mechanisms underlying anxiety.

One of the most common and significant symptoms for skin disorders is pruritus.Additionally,it serves as a significant catalyst for the exacerbation or reoccurrence of skin diseases.Pruritus seriously affects patients'physical and mental health,and even the quality of life.It brings a heavy burden to the patients,the families,even the whole society.The pathogenesis and regulation mechanisms for pruritus are complicated and have not yet been elucidated.Previous clinical studies have shown that itch worsens at night in scabies,chronic pruritus,atopic dermatitis,and psoriasis,suggesting that skin pruritus may change with circadian rhythm.Cortisol,melatonin,core temperature,cytokines,and prostaglandins are the main regulatory factors of the circadian rhythm of pruritus.Recent studies have shown that some CLOCK genes,such as BMAL1,CLOCK,PER,and CRY,play an important role in the regulation of the circadian rhythm of pruritus by regulating the Janus tyrosine kinase(JAK)-signal transducer and activator of transcription(STAT)and nuclear factor kappa-B(NF-κB)signaling pathways.However,the mechanisms for circadian clock genes in regulation of circadian rhythm of pruritus have not been fully elucidated.Further studies on the mechanism of circadian clock genes in the regulation of circadian rhythm of pruritus will lay a foundation for elucidating the regulatory mechanisms for pruritus,and also provide new ideas for the control of pruritus and the alleviation of skin diseases.

Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.