Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

Antibody (Ab) humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic Abs originated from animal models. Computational suggestions have long been desired, but available tools focused on immunogenicity calculation of whole Ab sequences and sequence segments, missing the individual residue sites. This study introduces Site-specific Immunogenicity for Therapeutic Antibody (SITA), a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody, but also individual residues, based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures. A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Ab-Ab structural complexes. On an independent testing dataset derived from 13 Ab-Ab structural complexes, SITA successfully predicted the epitope sites for Ab-Ab structures with a receiver operating characteristic (ROC)-area unver the ROC curve (AUC) of 0.85 and a precision-recall (PR)-AUC of 0.305 at the residue level. Furthermore, the SITA score can significantly distinguish immunogenicity levels of whole human Abs, therapeutic Abs and non-human-derived Abs. More importantly, analysis of an additional 25 therapeutic Abs revealed that over 70% of them were detected with decreased immunogenicity after modification compared to their parent variants. Among these, nearly 66% Abs successfully identified actual modification sites from the top five sites with the highest SITA scores, suggesting the ability of SITA scores for guide the humanization of antibody. Overall, these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To discuss the application effect of using a stone extractor balloon catheter to assist in crossing the anastomotic stenosis in treatment of anastomotic biliary stenosis after liver transplantation using endoscopic retrograde cholangiopancreatography(ERCP).Methods Clinical data of 48 patients who developed anastomotic biliary stenosis after liver transplantation and underwent ERCP treatment were collected.Upon unsuccessful use of a dilation catheter to cross the stricture,attempts were made to cross the anastomotic biliary stenosis by using a stone extractor balloon catheter.The success rate of the procedure was recorded,intraoperative conditions were observed,treatment outcomes and complications were analyzed.Results The main presenting symptoms in the 48 patients on admission were abdominal discomfort(32 patients),fever(7 patients),pruritus(4 patients),jaundice(3 patients),and no obvious symptoms(2 patients).Preoperative magnetic resonance cholangiopancreatography(MRCP)examination revealed isolated stricture of the anastomotic site in 35 cases,and stricture associated with stones in 13 cases.Using the stone extractor balloon catheter as a guide,guidewire crossing of the anastomotic stenosis was successful in 26 cases,resulting in a success rate of 54.17%(26/48).Through statistical analysis of the successful group and the failed group,there was a significant difference in whether the distal biliary dilatation between the two groups,and the difference was statistically significant(χ2 = 8.39,P = 0.004).In the 26 successfully treated cases,alanine transaminase(ALT),aspartate transaminase(AST),γ-glutamyl transpeptidase(γ-GT),alkaline phosphatase(ALP),and total bilirubin(TBiL)levels decreased significantly 48 hours after the procedure(P<0.05),and no serious complications occurred.Conclusion The use of a stone extractor balloon catheter significantly increases the success rate of crossing anastomotic stenosis in the treatment of anastomotic biliary stenosis after liver transplantation,especially in cases with distal dilatation of the common bile duct.This approach is safe and worth promoting.

OBJECTIVE To study the protective effect of saikosaponin b2(SSb2)on corticosterone(CORT)induced PC12 cell injury and its mechanism.METHODS ① PC12 cells were divided into the cell control group(24 h of culture with RPMI-1640 medium),CORT group(24 h of culture with CORT 100-800 μmol·L-1)and SSb2 group(24 h of culture with SSb2 1.5625,3.125,6.25,12.5,25,50 and 100 μmol·L-1).MTT assay was used to detect the cell survival rate.②PC12 cells were divided into the cell control group(24 h of culture with RPMI 1640 medium),model group(24 h of culture with CORT 400 μmol·L-1),and model+SSb2 group(3 h pretreatment with SSb2 1.5625,3.125,6.25,12.5 and 25 μmol·L-1,removal of the supernatant before cells were co-incubated with CORT 400 μmol·L-1 and corresponding concentrations of SSb2 for 24 h).MTT assay was used to detect the cell survival rate while micro-plate assay was used to detect the lactate dehydrogenase(LDH)leakage rate of PC12 cells.③PC12 cells were divided into the cell control group,model group and model+SSb2 12.5 μmol·L-1 group.AnnexinV-FITC/PI flow cytometry assay was used to detect PC12 cell apoptosis,ultra-perfor-mance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)cell metabonomics was used to detect metabolic profile changes and colorimetric assay was employed to detect the glutamic acid content and glutaminase activity in PC12 cells.RESULTS Compared with the cell control group,the cell viability decreased to(55±6)%(P<0.01)when the concentration of CORT was 400 μmol·L-1.When the concentration of SSb2 was higher than 50 μmol·L-1,there was significant toxicity to PC12 cells(P<0.01).②Compared with the cell control group,the cell survival rate was signif-icantly decreased(P<0.01),while the release rate of LDH was significantly increased(P<0.01)in the model group.Compared with the model group,the cell survival rate significantly increased(P<0.05,P<0.01),while the LDH release rate significantly decreased(P<0.01)in the model+SSb2 group.③ Com-pared with the cell control group,cell apoptosis was significantly increased in the model group(P<0.05).Compared with the model group,cell apoptosis was significantly decreased(P<0.05)in the model+ SSb2 group.Metabolomics results show that SSb2 significantly back-regulated nine differential metabo-lites of glutamate,creatine,N-acetylaspartate,L-tyrosine,citric acid,L-isoleucine,lactic acid,glutamine and choline.Further network analysis of the key metabolites regulated by SSb2 yielded five major metabolic pathways:D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,alanine,aspartate and glutamate metabolism,tyrosine metabolism and arginine biosynthesis.Compared with the cell control group,the content of glutamate and activity of glutaminase were significantly decreased in the model group(P<0.01).Compared with the model group,the content of glutamate(P<0.01)and activity of glutaminase(P<0.05)were significantly increased in the model+SSb2 group.CONCLUSION SSb2 has a neuroprotective effect on CORT-injured PC12 cells,and the mechanism of which is related to inhibition of apoptosis and regulation of metabolic disorders.

Hepatocellular carcinoma(HCC)has become the second leading cause of cancer-related death worldwide,ranking 6th among all tumors.Due to the lack of obvious early symptoms,most patients are diagnosed in the advanced stage,and the clinical benefits of surgical resection and hepatic artery chemoembolization and radiofrequency ablation are very limited.In recent years,the advent of immune-targeted therapies has revolutionized the systemic and systemic treatment of patients with advanced HCC,however,there is a lack of strong clinical evidence on the safety and efficacy of immune and targeted therapies for special populations,including patients with human immunodeficiency virus(HIV)infection,active autoimmune disease,decompensated cirrhosis(Child B or C),patients with diabetes-associated metabolic syndrome,patients with portal hypertension,vascular invasion,or portal vein thrombosis(PVT),and patients with liver transplantation(LT).This article reviews the current research progress of immune and targeted drugs in special populations.

Objective:To investigate the risk factors of pathological complete response(pCR)after neoadjuvant therapy for locally advanced gastric cancer(LAGC)and assess the value of gastric tumor markers for predicting pCR in LAGC patients.Methods:We retrospectively ana-lyzed the clinical and pathological characteristics of 213 patients who underwent radical gastrectomy and gastric tumor marker analysis after neoadjuvant therapy at The Chinse PLA General Hospital First Medical Center,between January 2020 and April 2024(20 and 193 cases in the pCR and non-pCR groups,respectively).The interrelationships among pCR,tumor markers,and clinicopathological features were compared,and independent risk factors for pCR were analyzed.A nomogram was constructed to predict the pCR.Results:Among 213 patients,20(9.4% )achieved pCR.Univariate analysis showed that age(P=0.067),tumor bed diameter(P<0.001),gastrin-17 levels(P=0.005),CA72-4 levels(P=0.073),pepsinogen ratio(P=0.024),and neoadjuvant immunotherapy(P=0.022)were strongly associated with pCR in LAGC pa-tients.Multivariate analysis showed that neoadjuvant immunotherapy,CA72-4 levels<2.5 U/mL,gastrin-17 levels<1.48 pmol/L,and tumor bed diameter<2.85 cm were independent predictive factors for pCR in LAGC patients(P<0.05).These indicators were incorporated into a nomogram prediction model;an receiver operating characteristic curve(ROC)was plotted with an AUC(95% CI)of 0.863(0.785-0.942).The calibration and decision curves suggested that the nomogram was well calibrated and had a good net benefit.Conclusions:Gastric tumor markers can effectively predict pCR after neoadjuvant therapy in LAGC patients.Our nomogram showed a good predictive ability for pCR.Thus,our findings can serve as a useful reference for clinical decision making for LAGC patients.

OBJECTIVES: This study examined the associations between adverse childhood experiences (ACEs) and diabetes within a social-ecological framework, incorporating personal and environmental unfavorable conditions during childhood from family, school, and community contexts. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (2014 life history survey and 2015 survey), including 9,179 participants aged ≥45 years. ACEs were collected through self-report questionnaires, and participants were categorized based on the number of distinct ACEs experienced (0, 1, 2, 3, or ≥4 ACEs). Diabetes was defined by biomarkers, self-reported diagnosis, and treatment status. Logistic regression was conducted to explore the associations between ACEs and diabetes. Subgroup analyses were conducted by gender, age, and obesity status. RESULTS: Compared with participants without ACEs, those exposed to any ACE (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40), 3 ACEs (OR, 1.32; 95% CI, 1.07 to 1.62) and ≥4 ACEs (OR, 1.29; 95% CI, 1.07 to 1.56) had an increased risk of diabetes. For each additional ACE, the risk of diabetes increased by about 5%. Regarding the source of ACEs, those originating from the family (OR, 1.23; 95% CI, 1.08 to 1.41) were associated with diabetes. In terms of specific ACE types, family members with substance abuse (OR, 1.23; 95% CI, 1.01 to 1.52), emotional abuse (OR, 1.28; 95% CI, 1.12 to 1.46), and poor parental relationship (OR, 1.25; 95% CI, 1.09 to 1.43) were associated with diabetes. CONCLUSIONS ACEs, particularly those originating from the family, were associated with diabetes. Interventions aimed at preventing and mitigating ACEs are essential for the early prevention of diabetes.

Objective:To explore the effect of scenario simulation combined with "finding fault" teaching method on prevention and control of nosocomial infection training in standardized residency training of cardiovascular surgery.Methods:A total of 31 residents trained in the Department of Cardiovascular Surgery, The First Affiliated Hospital of Naval Medical University from April 2018 to March 2019 were selected as the control group, and another 31 residents trained from April 2019 to March 2020 were selected as the study group. All subjects were required to receive nosocomial infection prevention and control training. The control group was given conventional teaching method, while the study group was given scenario simulation combined with "finding fault" teaching method, all of which were taught for 1 month. The theoretical and operational assessment results of nosocomial infection prevention and control after teaching, the clinical core competence related to nosocomial infection prevention and control after teaching, and the recognition rate of teaching mode were compared between the two groups. SPSS 25.0 was used for t test and chi-square test. Results:The scores of theoretical assessment [(91.29±6.64) vs. (86.73±6.02)] and operational assessment [(90.32±6.80) vs. (83.51±7.43)] of nosocomial infection prevention and control after teaching in the study group were higher than those in the control group, with statistical differences ( P<0.05). The scores of clinical core competence in learning initiative, doctor-patient communication, problem thinking and problem solving of nosocomial infection prevention and control knowledge after teaching in the study group were higher than those in the control group, with statistical differences ( P<0.05). The recognition rates of innovation, interest, effectiveness and practicability of the teaching mode in the study group were 83.87%, 96.77%, 90.32% and 93.55% respectively, while those in the control group were 61.29%, 58.06%, 67.74% and 74.19% respectively, which were higher in the study group than in the control group, with statistically significant differences ( P<0.05). Conclusion:In the training of prevention and control of nosocomial infection for standardized residency training in the department of cardiovascular surgery, scenario simulation combined with "fault finding" teaching method can improve the theoretical and practical examination results of the residents, enhance their clinical core competence related to nosocomial infection prevention and control, and reach a higher recognition rate of the teaching mode.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

OBJECTIVEThe purpose of this study was to investigate the influence of cryogenic treatment and age-hardening heat treatment on the micro-Vicker's hardness of palladium-silver dental alloys.

METHODSA low-gold content dental casting alloy composed of Ag-Pd-Cu-Au was prepared for this study. Experimental specimens according to standard requirements were prepared following a standard dental laboratory casting procedure, cast specimens were heated to 900 degrees C and quenched in ice water. The specimens were then divided into 4 groups. They were subsequently subjected to different treatments, including age-hardening heat treatment, cryogenic treatment, heat treatment combined with cryogenic treatment. The non-treated group was used as control. The micro-Vicker's hardness value was examined. The significance of correlation was analyzed.

RESULTSThe micro-Vicker's hardness of specimens after age-hardening heat treatment, cryogenic treatment, heat treatment combined with cryogenic treatment increased by 129%, 13% and 141%, respectively, compared with that of the non-treated control group. Conclusion Age-hardening heat treatment and cryogenic treatment were effective in elevating the hardness of Ag-Pd-Cu-Au alloy.