ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective To obtain the protective performance parameters of barium sulfate mortar against positron nuclide γ-rays, provide reference data for precise shielding calculations, and guide the design, evaluation, and construction of radiation shielding. Methods The FLUKA program was used to build a model for simulating the dose equivalent rate variation around points of interest under the irradiation of the most commonly used positron nuclide ¹⁸F with changes in the thicknesses of lead and barium sulfate mortar. The transmission curves of lead and barium sulfate mortar were fitted, and the half-value layer (HVL) and lead equivalence of barium sulfate mortar were calculated based on the fitted curves. Results The ambient dose equivalent rate coefficient of positron nuclide ¹⁸F was 1.339 4×10⁻¹ μSv·m²/MBq·h and the HVL for lead was 4.037 mm, with deviations of 0.043% and 1.53% compared to the values provided in the AAPM Report No. 108, respectively. The HVLs for γ-rays produced by ¹⁸F, using barium sulfate mortar with apparent densities of 4.20, 4.00, and 3.90 g/cm³ mixed with 35.2-grade cement in a 4∶1 mass ratio, were 2.914, 2.969, and 3.079 cm, respectively. The lead equivalences were 0.1385, 0.1360, and 0.1311 mmPb/mm, respectively. Conclusion The three types of barium sulfate mortar can provide good protection against γ-rays in positron imaging locations. As the apparent density of barium sulfate increases, its protective effect improves slightly but remains significantly better than common construction materials like concrete and solid bricks.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Diabetic cognitive dysfunction （DCD） is one of the complications of diabetes， which is characterized by impaired brain structure and progressively decreased learning and memory ability. With the increasing incidence of diabetes worldwide， DCD has become a serious medical and social problem. However， its pathophysiological mechanisms are not well understood. The occurrence and development of DCD involve multiple pathological links and mechanisms， and the prevention and treatment require multi-link and multi-target therapeutic measures. At present， there is no specific drug to prevent or improve DCD. Hypoglycemic drugs such as metformin and vigagliptin or anti-dementia drug including Donepezil are commonly used in clinical treatment to delay the occurrence and progression of cognitive dysfunction， but these drugs have a single target and obvious side effects. Traditional Chinese medicine has a long history in the prevention and treatment of diabetes and central cognitive diseases， and it has many unique advantages such as multiple components， multiple targets， side effects， and low price. A large number of studies have confirmed that traditional Chinese medicine has a significant prevention and treatment effect on DCD， which can improve insulin resistance， synaptic dysfunction， inflammation， oxidative stress， endoplasmic reticulum stress， and neuronal apoptosis by regulating phosphatidylin-ositol 3-kinase （PI3K）/protein kinase B （Akt）， advanced glycation end products （AGEs）/advanced glycation end products receptor （RAGE）/nuclear transcription factor-κB （NF-κB）， NOD-like receptor thermal protein domain associated protein 3 （NLRP3） inflammasome， and endoplasmic reticulum stress and nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathways. This article reviewed the effects and related mechanisms of traditional Chinese medicine on DCD in recent years， so as to provide a reference for the prevention and treatment of DCD by traditional Chinese medicine.

In this study, doxorubicin (DOX) was used as the model drug, new indocyanine green (IR820) as the photosensitizer, and temperature sensitive liposomes (TSL) as the carrier. H460-NCI photoheat-sensitive liposomes coated with cell membrane of human cell lung cancer (DOX-IR820-TSL@CCM) for highly effective multi-pathway tumor targeting in chemical-photothermal therapy and photodynamic therapy. DOX-IR820-TSL was prepared by reverse evaporation, cancer cell membrane (CCM) was prepared by lysis, crushing and centrifugation, and DOX-IR820-TSL@CCM was prepared by nanomembrane extrusion. The drug-loading conditions of DOX-IR820-TSL were finally determined: the ratio of organic phase to aqueous phase was 4.02, the dosage of dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) was 10.04 mg, and the lipid ratio was 0.12, and the significant phase transition temperature (T_m) of DOX-IR820-TSL was 43.05 ℃. The average particle size of DOX-IR820-TSL@CCM was 153.4 nm, the PDI was 0.279, and the zeta potential was -26.2 mV. The transmission electron microscope (TEM) image shows a homogeneous spherical structure and a translucent film layer. Under near-infrared irradiation, the drug release rate reaches 63.98%, which has adjustable photothermal conversion capacity and the ability to generate reactive oxygen species. Through SDS-PAGE electrophoresis, Western blot, cytotoxicity experiments and cell uptake experiments, it was proved that the design of cell membrane coating can well retain CD47, N-cadherin, CD44, CD326 and other related functional proteins, so that DOX-IR820-TSL@CCM has good immune evasion, homologous adhesion and homologous targeting. In this paper, DOX-IR820-TSL@CCM with camouflage properties and tumor targeting properties were successfully prepared, which can be used as a promising synergistic therapeutic diagnostic platform for future lung cancer treatment. All animal research programs have been approved by the Animal Ethics Committee of Heilongjiang University of Chinese Medicine (number: 2022121011).

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.