Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Fibrosis is a pathological condition characterized by the excessive deposition of extracellular matrix due to the imbalance between injury and repair.It can affect multiple organs,including the heart,lungs,liver,kidneys,and pancreas.The progression of fibrosis is usually slow and difficult to reverse,and it can severely impair organ functions.In industrialized countries,deaths caused by fibrosis account for up to 45％,resulting in a tremendous disease burden.Thus,there is an urgent need for drugs that can reverse or delay the progression of fibrosis.In recent years,remarkable progress has been made in the research on the pathogenesis of fibrosis in different organs,and relevant drugs targeting fibrosis are also under active development.This article briefly summarizes the drugs currently marketed and drugs at the clinical trial stage for treating fibrosis.

Comprehensive performance appraisal,continuous optimization of performance appraisal indicators,reform of internal performance appraisal methods,and linking the appraisal results to salary allocation are important measures for the high-quality development of public hospitals.It is based on the performance allocation mechanism improvement in case hospital under the requirements of high-quality development.The implementation of performance reform practice based on incremental assessment has achieved the social benefits improvement,income structure optimization,performance distribution equity improvement,and more refined management of disciplines and other management objectives,with a view to providing lessons and references for medical colleagues to follow up to deepen the performance reform and improve the performance distribution.

Objective:To clarify the morphological relationship between the upper airway and TMJ in patients with normal-angle skeletal Ⅱ and skeletal Ⅰ malocclusion.Methods:30 skeletal class Ⅰ and 22 skeletal class Ⅱ patients with normal-angle were included.CBCT examination was performed,and Mimics 21.0 software was used to conduct 3D reconstruction and measurements of the samples.Data was analyzed by using independent t-test and the Pearson correlation test.Results:12 measurements,including the sagittal diameter of nasopharyngeal segment,the sagittal,coronal diameter,minimum cross-sectional area,the volume of palato-pharyngeal segment and glossopharyngeum segment,the total volume of upper airway,posterior oblique slope of the articular eminence and the length of the condylar showed significant differences between skeletal Ⅱ and skeletal Ⅰ subjects with normal-angle(P＜0.05).The posterior oblique slope of the articular eminence showed a positive correlation with the sagittal diameter of the palatopharyngeal segment,volume and minimum cross-sectional area of glossopharyngeum lingual segment(P＜0.05).The liner ratio showed a negative correction with the coronal diameter of palatopharyngeal and glossapharyngeal segment as well as minimum cross-section area of glos-sapharyngeal segment(P＜0.05).Conclusion:The structure of upper airway is correlated with that of TMJ.Differences in the upper airway are statistically significant between skeletal Ⅱ and skeletal Ⅰ malocclusion with normal-angle(P＜0.05).

Objective:To clarify the morphological relationship between the upper airway and TMJ in patients with normal-angle skeletal Ⅱ and skeletal Ⅰ malocclusion.Methods:30 skeletal class Ⅰ and 22 skeletal class Ⅱ patients with normal-angle were included.CBCT examination was performed,and Mimics 21.0 software was used to conduct 3D reconstruction and measurements of the samples.Data was analyzed by using independent t-test and the Pearson correlation test.Results:12 measurements,including the sagittal diameter of nasopharyngeal segment,the sagittal,coronal diameter,minimum cross-sectional area,the volume of palato-pharyngeal segment and glossopharyngeum segment,the total volume of upper airway,posterior oblique slope of the articular eminence and the length of the condylar showed significant differences between skeletal Ⅱ and skeletal Ⅰ subjects with normal-angle(P＜0.05).The posterior oblique slope of the articular eminence showed a positive correlation with the sagittal diameter of the palatopharyngeal segment,volume and minimum cross-sectional area of glossopharyngeum lingual segment(P＜0.05).The liner ratio showed a negative correction with the coronal diameter of palatopharyngeal and glossapharyngeal segment as well as minimum cross-section area of glos-sapharyngeal segment(P＜0.05).Conclusion:The structure of upper airway is correlated with that of TMJ.Differences in the upper airway are statistically significant between skeletal Ⅱ and skeletal Ⅰ malocclusion with normal-angle(P＜0.05).

Comprehensive performance appraisal,continuous optimization of performance appraisal indicators,reform of internal performance appraisal methods,and linking the appraisal results to salary allocation are important measures for the high-quality development of public hospitals.It is based on the performance allocation mechanism improvement in case hospital under the requirements of high-quality development.The implementation of performance reform practice based on incremental assessment has achieved the social benefits improvement,income structure optimization,performance distribution equity improvement,and more refined management of disciplines and other management objectives,with a view to providing lessons and references for medical colleagues to follow up to deepen the performance reform and improve the performance distribution.

Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy. This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles (MON) loaded with 2-deoxy-D-glucose (2-DG). Thanks to the tumor-targeting ability of the platelet membranes, PMD can target and aggregate to the tumor site, which is internalized by tumor cells. Within tumor cells overexpressing GSH, MON reacts with GSH to degrade and release 2-DG. This step initially depletes the intracellular GSH content. The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate (ATP) production, ultimately leading to secondary GSH consumption. This nanodrug combines dual GSH depletion, starvation therapy, and RT to promote immunogenic cell death and stimulate the systemic immune response. In the bilateral tumor model in vivo, distal tumor growth was also well suppressed. The proportion of mature dendritic cells (DC) and CD8⁺ T cells in the mice was increased. This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.

Radiotherapy(RT)is one of the most common treatments for cancer.However,intracellular glutathione(GSH)plays a key role in protecting cancer from radiation damage.Herein,we have developed a platelet membrane biomimetic nanomedicine(PMD)that induces double GSH consumption to enhance tumor radioimmunotherapy.This biomimetic nanomedicine consists of an external platelet membrane and internal organic mesoporous silica nanoparticles(MON)loaded with 2-deoxy-D-glucose(2-DG).Thanks to the tumor-targeting ability of the platelet membranes,PMD can target and aggregate to the tumor site,which is internalized by tumor cells.Within tumor cells overexpressing GSH,MON reacts with GSH to degrade and release 2-DG.This step initially depletes the intracellular GSH content.The subsequent release of 2-DG inhibits glycolysis and adenosine triphosphate(ATP)production,ultimately leading to secondary GSH consumption.This nanodrug combines dual GSH depletion,starvation therapy,and RT to promote immunogenic cell death and stimulate the systemic immune response.In the bilateral tumor model in vivo,distal tumor growth was also well suppressed.The proportion of mature dendritic cells(DC)and CD8+T cells in the mice was increased.This indicates that PMD can promote anti-tumor radioimmunotherapy and has good prospects for clinical application.

【Objective】 To investigate the effects of preoperative ureteroscopy (URS) on the intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). 【Methods】 The clinical data of 241 UTUC patients treated during May 2012 and Jan.2020 in the Second Hospital of Laozhou University were retrospectively analyzed. The patients were divided into URS before RNU group (URS group) and non-URS before RNU group (non-URS group). The cumulative IVR rate, progression-free survival (PFS) and overall survival (OS) after RNU were compared, and the survival curve was drawn. Cox proportional hazards models were used to assess risk factors affecting IVR. 【Results】 Of the 241 patients, 64 (26.6%) were included in the URS group and 177 (73.4%) in the non-URS group. In the URS group, 49 underwent biopsy and 15 did not. All patients were followed up for a median of 44 (3 to 122) months, with a median time to recurrence of 12 (3 to 56) months. IVR occurred in 18 patients (28.1%) in the URS group and 25 (14.1%) in the non-URS group. Kaplan-Meier survival analysis showed that the cumulative IVR rate was higher in the URS group than in the non-URS group (all P<0.05), regardless of whether patients had a history of bladder cancer (BC) or not, while PFS was lower in the URS group than in the non-URS group (P=0.007). Cox multivariate regression analysis showed that URS (P=0.031) and complicated renal pelvis tumor and ureteral tumor (P=0.004) were independent risk factors for IVR. 【Conclusion】 Preoperative URS increases the incidence of IVR in patients with UTUC, and routine preoperative use of URS is not recommended.