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.

Objective To explore the application of evidence-based nursing based on mind mapping in patients undergoing knee arthroscopic surgery.Methods Ninety patients who underwent arthroscopic surgery in Dongzhimen Hospital,Beijing University of Chinese Medicine from June 2021 to January 2023 were selected for prospective study.They were randomly assigned to study group or control group according to the random number table,with 45 cases in each group.The control group was given routine nursing,and the study group was given evidence-based nursing based on mind mapping.The nursing care continued until one month after discharge.Psychological resilience score,pain degree[(visual analogue scale,VAS)score],hospitalization time,hospital knee score(HSS)score,postoperative complications and satisfaction degree at discharge were compared between the two groups.Results Repeated measures showed that there were significant differences in the time-point effect,intergroup effect and interaction effect of psychological resilience score and HSS score between the two groups(P<0.05),and the psychological resilience score and HSS score of the study group were higher than those of the control group(P<0.05).The VAS score at discharge and hospital stay of the study group were superior to those of the control group(P<0.05).The incidence of postoperative complications in the study group was lower than that in the control group(2.22%vs 17.78%,P<0.05).The degree of patients'satisfaction in the study group was higher than that in the control group(P<0.05).Conclusion Evidence-based nursing based on mind mapping can effectively improve psychological resilience,relieve postoperative pain,increase the range of motion of the knee,promote recovery,reduce postoperative complications and improve clinical satisfaction.

The transformation from inflammation to cancer is a complex pathological process, in which the inflammatory state progresses to the formation of malignant tumors. Chronic pancreatitis (CP) is a progressively inflammatory and fibrosing disease, predominantly featuring acinar cell atrophy owing to the cellular damage and fibrosis of the pancreatic parenchyma. This review centers on elucidating how prolonged exposure to a chronic inflammatory environment prompts adaptive changes in acinar cells, which may ultimately lead to their conversion into cancerous cells. By delving into the pivotal role of acinar-to-ductal metaplasia, this article investigates the multi-stage pathway of CP progression into pancreatic cancer, as well as the underlying molecular regulatory networks. We aim to light on the profound mechanisms of CP's inflammation-driven carcinogenic transformation, and thus provide a scientific foundation for devising innovative preventive strategies and therapeutic interventions targeted at mitigating or halting this lethal conversion process.

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.

Familial pheochromocytoma belongs to autosomal dominant inheritance, and has complex and variable clinical manifestations. A child with bilateral PHEO was admitted to our hospital. His grandmother, father and brother were all diagnosed with PHEO, and his aunt was diagnosed with paraganglioma. The child underwent laparoscopic left partial adrenalectomy and open surgery for the contralateral tumor, and was in good postoperative condition. The blood pressure returned to normal and there was no local recurrence and metastasis during the follow-up of 8 months after the second operation.

Objective:By analyzing the clinical data of patients with primary duodenal adenocarcinoma (PDA), the risk factors affecting the postoperative prognosis of PDA patients were discussed.Methods:The clinical data of 191 patients diagnosed with PDA in Peking University First Hospital from Jan 2009 to Dec 2022 were collected. The survival rate was calculated and the survival curve was plotted by Kaplan-Meier method. Univariate analysis was performed by Log-Rank test, and multivariate analysis was performed by COX proportional hazards regression model to obtain independent risk factors.Results:The median age of onset in patients with PDA is 65 years old, and the most common symptoms are abdominal pain and abdominal distension. Prognostic analysis showed that the survival rates at 1, 3 and 5 years were 73.8%, 44.6%, and 23.0%. The analysis of Cox risk proportional regression model showed that preoperative CA19-9 level, depth of tumor invasion, degree of differentiation, TNM stage, and surgical mode were independent risk factors for the prognosis of PDA (all P<0.01). Conclusion:The overall incidence of PDA is low, but the prognosis is rather poor. Multvariable factors are associated with its prognosis and surgery is still the mainstay for hope of cure.

【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.

Depression is one of the common and serious complications after stroke. Post-stroke depression (PSD) is associated with poor outcomes and increased mortality. The American Heart Association/American Stroke Association guidelines for the early management of patients with acute ischemic stroke recommend that pharmacological therapy should be administered to patients with PSD. This article reviews the pharmacological therapy for PSD.