Interfering hepatitis B virus (HBV) capsid assembly holds promise as a therapeutic approach for chronic hepatitis B (CHB). Novel anti-HBV agents are urgently needed to overcome drug resistance challenges, with targeted protein degradation (TPD) emerging as a hopeful strategy. Herein, we report the first degradation of HBV core protein (HBC), a multifunctional structural protein, using small-molecule degraders developed by hydrophobic tagging (HyT) technology. Structure-activity relationship (SAR) analysis identified compound HyT-S7, featuring an adamantyl group, exhibiting potent inhibitory activity (EC₅₀ = 0.46 μmol/L, HepAD38 cells) and degradation ability (DC₅₀ = 3.02 ± 0.54 μmol/L) in a dose- and time-dependent manner. Mechanistic studies demonstrated that the autophagy-lysosome pathway was a potential driver of HyT-S7-induced HBC degradation. Remarkably, HyT-S7 effectively degraded 11 drug-resistant mutants, including highly resistant strains P25G and T33N, to Phase III drug GLS4. Furthermore, cellular thermal shift assay, surface plasmon resonance assay, and molecular dynamics simulations revealed the precise mode of HyT-S7 binding to HBC with the adamantyl group potentially mimicking protein misfolding to facilitate HBC degradation. This first proof-of-concept study highlights the potential of HyT-mediated TPD in HBC as a promising avenue for discovering novel HBV and other antiviral agents with favorable drug resistance profiles.

Objective To utilize the dental implant robot in the clinical instruction of oral implantology in order to popularize the technology and serve the medical education.Methods The effectiveness of the robotics teaching approach was assessed through a questionnaire.Results The dental implant robot technology has certain advantages in the clinical teaching of oral implant majors.Conclusion With the increasing popularity of digital implantation,the emerging dental implant robot has a wide range of applications and many advantages.It is very necessary to introduce it into the clinical teaching of oral implant majors.

Objective:Hearing loss can seriously affect mental health status, and this study aims to investigate the influence of hearing health status on depressive symptoms among middle-aged and older individuals in the community.Methods:From June to December 2023, a stratified random sampling method was employed to select 1 238 community-dwelling middle-aged and elderly people aged 45 years and above from four cities (Hangzhou, Shanghai, Baoding, and Zhengzhou) as research subjects. A questionnaire survey was conducted to collect the subjects′ basic information, hearing health status [assessed by the Hearing Handicap Inventory for Adults-Screening Version (HHIA-S)], and depressive symptoms [assessed by the Geriatric Depression Scale-15 (GDS-15)]. T-tests, rank-sum tests and chi-square tests were used for univariate analysis, while, multiple linear regression and binary Logistic regression were applied to analyze the relationship between hearing health status and depressive symptoms.Results:A total of 1 183 community-dwelling middle-aged and elderly people aged 45 years and above were included in the final analysis (464 males and 719 females, aged from 45 to 96 years). The detection rate of hearing loss was 35.3%(418/1 183), while, the detection rate of depressive symptoms was 9.89%(117/1 183). Age, level of interaction with children, self-rated health, perceived loneliness, and hearing health significantly influenced depressive symptoms among older adults residing in the community ( P<0.05). Individuals with moderate to severe hearing loss ( β=2.04, 95% CI: 1.47, 2.62) exhibited higher GDS-15 scores compared to those without hearing impairment. Furthermore, after correcting for sex, age, marital status, monthly per capita family income, education, residence, smoking status, alcohol use, use of psychotropic medication (anxiolytic or depressant), number of illness, self-health assessment, and autonomy, middle-aged and older adults with mild to moderate hearing loss ( OR=2.89, 95% CI: 1.76, 4.88) and severe hearing loss ( OR=5.79, 95% CI: 3.05, 11.01) demonstrated an increased likelihood of experiencing depression. Conclusions:The degree of hearing loss in community-dwelling middle-aged and elderly individuals is closely associated with the risk of depressive symptoms. Therefore, it is imperative to enhance hearing health screening and to provide mental health support to individuals with hearing loss, in order to mitigate the onset and progression of depressive symptoms.

Objective:To observe the clinical efficacy of snake-like moxibustion combined with aconitum ointment based on routine Western medication in the treatment of ankylosing spondylitis(AS)of cold-dampness blockage pattern,and to evaluate its effects on traditional Chinese medicine(TCM)symptoms,serum Dickkopf-1 protein(DKK-1)level,and disease activity.Methods:A total of 120 AS patients were selected as research subjects and randomly divided into an observation group and a control group according to the random number table method,with 60 cases in each group.The control group was treated with oral sulfasalazine enteric-coated tablets as conventional therapy;the observation group was additionally treated with snake-like moxibustion combined with external application of aconitum ointment based on the intervention in the control group.After 4 weeks of consecutive treatment in both groups,the total effective rate was compared.Changes in TCM symptom scores,spinal pain visual analog scale(VAS)score,overall evaluation VAS score,Bath ankylosing spondylitis disease activity index(BASDAI)score,Bath ankylosing spondylitis functional index(BASFI)score,erythrocyte sedimentation rate(ESR),and serum levels of C-reactive protein(CRP),tumor necrosis factor(TNF)-α,and DKK-1 were observed.Results:The total effective rate in the observation group was higher than that in the control group,and the difference was statistically significant(P<0.05).After treatment,the scores of TCM symptoms,spinal pain VAS,overall evaluation VAS,BASDAI,and BASFI,as well as ESR,serum levels of CRP,TNF-α,and DKK-1 in both groups were lower than those before treatment,with statistically significant differences within groups(P<0.05);all indicators in the observation group were lower than those in the control group,with statistically significant differences between groups(P<0.05).Conclusion:Based on routine Western medication treatment,the addition of snake-like moxibustion combined with external application of aconitum ointment yields better therapeutic efficacy than Western medication alone in the treatment of AS.It can significantly improve clinical symptoms,control inflammation,and down-regulate the serum DKK-1 level.

Objective To evaluate the value of modified percutaneous endoscopic gastrostomy(PEG)for patients with amyotrophic lateral sclerosis(ALS)and dysphagia.Methods From January 2018 to December 2023,47 patients with ALS were treated with modified PEG in our hospital.The surgery was performed under local anesthesia.The patients were placed in a semi-seated position,and the surgeon performed surgery with an ultra-fine endoscope through oral entrance to the stomach.Results The modified PEG were successfully completed in all the 47 cases.The operation time was5-20 min[mean,(10.3±1.7)min].The postoperative hospitalization lasted for2-8 d(mean,2.8 d).Postoperative complications occurred in6 cases(12.8%),including aspiration pneumonia in4 cases(8.5%)and incision infection in2 cases(4.3%).The body mass index was17.06±0.89 before PEG and 18.15±0.81 at 3 months after PEG,with significant difference(t=-10.373,P=0.000).Conclusion For ALS patients with dysphagia,modified PEG is feasible,which significantly improves nutritional status of patients.

Objective:A retrospective study was conducted to investigate the safety of Percutaneous Endoscopic Gastrostomy(PEG)in elderly patients with Amyotrophic Lateral Sclerosis(ALS)and to identify the factors influencing major complications.The aim is to establish a more robust foundation for optimizing both the procedure and its timing, thereby enhancing the evidence base for refining the surgical approach.Methods:We retrospectively collected clinical data from elderly ALS patients(≥60 years old)who underwent PEG at Peking University Third Hospital between January 2006 and January 2024.This dataset includes information on general health conditions, the progression of ALS, comorbidities, surgical details, and related complications.Additionally, we analyzed the postoperative complications experienced by the included patients, focusing specifically on the risk factors associated with aspiration pneumonia.Results:A total of 140 patients were included in the study, with a mean age of 68.2±5.9 years.Among these, 69 were male(49.3%)with a mean age of 68.4±6.5 years, and 71 were female(50.7%)with a mean age of 67.7±6.0 years.Successful outcomes were observed in 139 cases(99.3%).One case was not completed due to respiratory arrest caused by intraoperative aspiration.Postoperative complications occurred in 36 cases(25.7%), which included 9 cases of wound infection(6.4%), 1 case of abdominal infection(0.7%), 21 cases of aspiration pneumonia(15.0%), 1 case of local fistula leakage(0.7%), 2 cases of transient fever(1.4%), and 2 cases of death during hospitalization(1.4%).Both univariate and multivariate analyses indicated that an onset duration of ≤1 year( P=0.020)and a half-sitting position( P=0.022)significantly influenced the occurrence of aspiration pneumonia, acting as protective factors( β<0, OR<1). Conclusions:PEG is a safe method for providing enteral nutrition to elderly patients with ALS.While most complications associated with the procedure are mild and can be managed, Aspiration pneumonia remains a common and serious complication.However, early surgical intervention and the use of a semi-seated position during the procedure can help reduce the incidence of aspiration pneumonia.

Pinellia ternata， belonging to the Pinellia genus within the Araceae family， is a medicinal plant due to its tubers. There are severe issues with unclear germplasm and mixed varieties in its cultivation， necessitating urgent new variety protection efforts. The distinctness， uniformity， and stability （DUS） testing of the plant variety is the basis for protecting new plant varieties， and the DUS test guidelines are the technical basis for DUS testing. To develop the DUS test guidelines for P. ternata， agronomic traits of 229 germplasm of P. ternata were observed and measured during its two growth stages over the years， and each character was graded and described. A total of 38 traits were selected as the test traits of the DUS test guideline for P. ternata. There were three plant traits， 19 leaf traits， six flower traits， two fruit traits， two tuber traits， five bulbil traits， and one ploidy trait. These traits could be divided into 22 quality characters， 12 quantitative characters， and four pseudo-quantitative characters， as well as seven groups， including plants， leaves， flowers， fruit， tubers， bulbils， and ploidy. By searching for standard traits， 10 standard varieties were ultimately determined. Preparing these guidelines will have great significance for reviewing and protecting P. ternata varieties， safeguarding breeders' rights， and promoting the development of the P. ternata industry.

Objective To assess the effect of early nutritional intervention on the patients with respiratory diseases at nutritional risk. Methods A total of 130 patients with respiratory disease who were hospitalized in Shanghai Fifth People’s Hospital, Fudan University between May 2023 and December 2024 and had a nutritional risk screening 2002 score ≥3 points. Based on the initiation time of nutritional intervention, patients were divided into an early group (≤5 days, n＝65) and a late group (＞5 days, n＝65). Results In the early group, prealbumin (P-ALB) and retinol-binding protein (RBP) levels were significantly higher (P＜0.01), C-reactive protein (CRP), procalcitonin (PCT) levels were significantly lower after intervention (P＜0.05). Compared with the late group, the hospital costs were lower and hospital stays were shorter in the early group (P＜0.001). Spearman analysis showed ALB, P-ALB, and total protein (TP) were negatively correlated with hospital costs (r＝－0.37, －0.20, and－0.22, P＜0.05). RBP, ALB, P-ALB, and lymphocyte count (LYM) were negatively correlated with CRP (r＝－0.30, －0.26, －0.37, －0.18, P＜0.01), RBP, ALB, P-ALB, hemoglobin (HB), and TP were negatively correlated with PCT (r＝－0.23,－0.36, －0.40, －0.30, －0.19, P＜0.05). Conclusions For patients with respiratory diseases, early nutritional assessment should be underwent, and for patients with nutritional risk screening 2002 score ≥3 points, early nutritional intervention could improve the nutritional status and alleviate inflammatory response, promote recovery, shorten the hospital stays.

Objective: To analyze the space time characteristics of poor vision among primary and secondary school students in Chengdu, in order to provide the reference for formulating myopia prevention and control policies for students. Methods: The data relating to poor vision among primary and secondary school students in Chengdu from 2021 to 2023 were sourced from the Sichuan Students Physical Health Big Data Center. The districts and counties of Chengdu were divided into three circles, including the main urban area, suburban districts and counties, and suburban districts and counties. The Chi square test was used for inter group comparison, and the Cochran-Armitage test was used to analyze the trend of changes. Global and local Moran s I were used to analyze spatial clustering. Results: The detection rates of poor vision among primary and secondary school students in Chengdu from 2021 to 2023 were 62.47%, 61.61% and 60.78%, respectively, showing a decreasing trend ( Z=-32.01, P <0.01). For each year, the higher detection rate of poor vision among students was detected in the higher level of education, and differences were statistically significant ( χ 2=161 549.47, 173 471.87, 233 459.09, P <0.01). The rate of poor vision among primary and secondary school students gradually decreased from the central districts and counties of Chengdu to the surrounding districts and counties for each year, and the differences were statistically significant ( χ 2=299.20, 776.22, 633.16, P <0.01). The spatial autocorrelation analysis showed that the first circle of Chengdu City was mainly characterized by high-high agglomeration ( P <0.01), with the rate of poor vision among primary school students in Wuhou District in 2023 exhibiting a low-high anomaly. The third circle was mainly characterized by low-low aggregation ( P <0.01), while the spatial clusterings of the second circle was not significant ( P >0.05). Conclusions The myopia prevention and control work in Chengdu has achieved preliminary results. It should continue to consolidate existing achievements and implement targeted myopia prevention and control measures based on regional characteristics.

Objective To explore the therapeutic effect and mechanism of baicalin on gestational diabetes mellitus(GDM)rats.Methods A GDM rat model was induced by a high-fat high-glucose diet combined with Streptozotocin(STZ)Injection.Forty modeled successfully rats were randomly divided into model group,Metformin group,low-and high-dose baicalin group and high-dose baicalin+ML385[nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor]group,with 8 rats in each group,in addition,the normal group(8 healthy rats)was set up.After group intervention,fasting blood glucose(FBG),fasting insulin(FINS),and homeostasis model assessment of insulin resistance(HOMA-IR)levels were measured.Serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP)were detected.The levels of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),and catalase(CAT)in liver tissue were measured.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum inflammatory factors,including tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β),and interleukin 6(IL-6).Hematoxylin-eosin(HE)staining was used to observe liver histopathological changes.Western Blot was used to detect the protein expression levels of Nrf2 and heme oxygenase-1(HO-1)in rat liver tissue.Results Compared with the normal group,the model group showed significantly increased levels of FBG,FINS,HOMA-IR,ALT,AST,ALP,TNF-α,IL-1β,IL-6 and MDA(P＜0.05),while the levels of SOD,CAT,GSH-Px,and the expression levels of Nrf2 and HO-1 were significantly decreased(P＜0.05).HE staining of liver tissue revealed disordered cell arrangement and extensive cell degeneration and necrosis.Compared with the model group,the Metformin group,high-dose baicalin group,and high-dose baicalin+ML385 group showed significantly decreased levels of FBG,FINS,HOMA-IR,ALT,AST,ALP,TNF-α,IL-1β,IL-6 and MDA(P＜0.05),while the levels of SOD,CAT,GSH-Px,and the expression levels of Nrf2 and HO-1 were significantly increased(P＜0.05).The structure of liver sinusoids improved,and necrotic cells were reduced.Compared with the low-dose baicalin group,the high-dose baicalin group showed significantly decreased levels of FBG,FINS,HOMA-IR,ALT,AST,ALP,TNF-α,IL-1β,IL-6 and MDA(P＜0.05),while the levels of SOD,CAT,GSH-Px,and the expression levels of Nrf2 and HO-1 were significantly increased(P＜0.05).The structure of liver sinusoids improved,and necrotic cells were reduced.Compared with the high-dose baicalin group,the high-dose baicalin+ML385 group showed a reversal in the above indicators(P＜0.05).Conclusion Baicalin can alleviate oxidative stress injury in GDM rats by activating Nrf2 and HO-1 expression.