ObjectiveUlcerative colitis is a prevalent immunoinflammatory disease. Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis. The actin cytoskeleton contributes to regulating the proliferation, differentiation, and migration of Th17 and Treg cells. Wdr63, a gene containing the WD repeat domain, participates in the structure and functional modulation of actin cytoskeleton. Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition. This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis. MethodsWe constructed Wdr63^-/- mice, induced colitis in mice using dextran sulfate sodium salt, collected colon tissue for histopathological staining, collected mesenteric lymph nodes for flow cytometry analysis, and collected healthy mouse feces for microbial diversity detection. ResultsCompared with wild-type colitis mice, Wdr63^-/- colitis mice had a more pronounced shortening of colonic tissue, higher scores on disease activity index and histological damage index, Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes, a lower level of anti-inflammatory cytokine IL-10, and a higher level of pro-inflammatory cytokine IL-17A. In addition, WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis. It maintains the balance of Bacteroidota and Firmicutes, promoting the formation of beneficial intestinal bacteria linked to immune inflammation. ConclusionWdr63 deletion aggravates ulcerative colitis in mice, WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.

Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

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.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

Adaptive immunity is a critical component of the human immune system, playing an essential role in identifying antigens and orchestrating a tailored immune response. This review delves into the significant strides made in the development of epitope prediction tools, their integration into vaccine design, and their pivotal role in enhancing immunotherapy strategies. The review emphasizes the transformative potential of these tools in refining our understanding and application of immune responses. Adaptive immunity distinguishes itself from innate immunity by its ability to recognize specific antigens and remember past infections, leading to quicker and more effective responses upon subsequent exposures. This facet of immunity involves complex interactions between various cell types, primarily B cells and T cells, which recognize distinct epitopes presented by antigens. Epitopes are small sequences or configurations on antigens that are recognized by the immune receptors on B cells and T cells, acting as the focal points of immune recognition and response. Epitopes can be broadly classified into two types: linear (or sequential) epitopes and conformational (or discontinuous) epitopes. Linear epitopes consist of a sequence of amino acids in a protein that are recognized by B cells and T cells in their primary structure form. Conformational epitopes, on the other hand, are formed by spatially distinct amino acids that come together in the tertiary structure of the protein, often recognized by the immune system only when the protein folds into its native conformation. The role of epitopes in the immune response is critical as they are the primary triggers for the activation of B cells and T cells. When an epitope is recognized, it can stimulate B cells to produce antibodies, mobilize helper T cells to secrete cytokines, or prompt cytotoxic T cells to kill infected cells. These actions form the basis of the adaptive immune response, tailored to eliminate specific pathogens or infected cells effectively. The prediction of B cell and T cell epitopes has evolved with advances in computational biology, leading to the development of several sophisticated tools that utilize a variety of algorithms to predict the likelihood of epitope regions on antigens. Tools employing machine learning methods, such as support vector machines (SVMs), XGBoost, random forest, analyze large datasets of known epitopes to classify new sequences as potential epitopes based on their similarity to known data. Moreover, deep learning has emerged as a powerful method in epitope prediction, leveraging neural networks capable of learning high-dimensional data from vast amounts of immunological inputs to identify patterns that may not be evident to other predictive models. Deep learning models, such as convolutional neural networks (CNNs), recurrent neural networks (RNNs) and ESM protein language model have demonstrated superior accuracy in mapping the nonlinear relationships inherent in protein structures and epitope interactions. The application of epitope prediction tools in vaccine design is transformative, enabling the development of epitope-based vaccines that can elicit targeted immune responses against specific parts of the pathogen. These vaccines, by focusing the immune response on highly specific regions of the pathogen, can offer high efficacy and reduced side effects. Similarly, in cancer immunotherapy, epitope prediction tools help identify tumor-specific antigens that can be targeted to develop personalized immunotherapeutic strategies, thereby enhancing the precision of cancer treatments. The future of epitope prediction technology appears promising, with ongoing advancements anticipated to enhance the precision and efficiency of these tools further. The integration of broader immunological data, such as patient-specific immune profiles and pathogen variability, along with advances in AI and machine learning, will likely drive the development of more adaptive, robust, and clinically relevant prediction models. This will not only improve the effectiveness of vaccines and immunotherapies but also contribute to our broader understanding of immune mechanisms, potentially leading to breakthroughs in the treatment and prevention of multiple diseases. In conclusion, the development and refinement of epitope prediction tools stand as a cornerstone in the advancement of immunological research and therapeutic design, highlighting a path toward more precise and personalized medicine. The ongoing integration of computational models with experimental immunology holds the promise of revolutionizing our approach to combating infectious diseases and cancer.

Statistical analysis was conducted on the quantity of Chinese medicine material and sliced herbal medicine,the species types and medicinal parts of Chinese medicine material and sliced herbal medicine,and the quantity and composition of Chinese patent medicines and single-herb preparations in Chinese Pharmacopoeia of the 2020 edition.The statistical results are available on the web site(http://itcm.hzau.edu.cn/yd/zgyd.htm)for reference.The analysis results showed that:(1)Chinese Pharmacopoeia(Part I)contained a total of 616 kinds of Chinese medicine material and sliced herbal medicine and 47 kinds of plant oils and extracts.The 616 kinds of Chinese medicine material and sliced herbal medicine originated from plants,animals,minerals,microorganisms,artificial or synthetic raw materials,human-sourced products,and products having the origin of both animal and plants.Of the 47 kinds of plant oils and extracts,46 were made from plant sources,and the remaining one,i.e.Cornu Bubali concentrated powder,was made from the animal sources.(2)A total of 421(73.60%)from the 616 kinds of Chinese medicine material and sliced herbal medicine originated from the single species,96(16.78%)originated from 2 kinds of species,40(6.99%)originated from 3 kinds of species,11(1.92%)originated from 4 kinds of species,2(0.35%)originated from 5 kinds of species,and 2(0.35%)originated from 6 kinds of species.Of the 47 kinds of plant oils and extracts,34 originated from the single species,5 originated from 2 kinds of species and 5 originated from 3 kinds of species.(3)The Chinese Pharmacopoeia(Part I)contained a total of 1 605 Chinese patent medicines and single-herb preparations.Except that the composition of Yunnan Baiyao Powder and Yunnan Baiyao Capsules was not issued,the remaining 1 603 types of Chinese patent medicines and single-herb preparations involved a total of 14 329 kinds of medicinal materials.The Chinese medicines with the leading 20 frequency used in the Chinese patent medicines and single-herb preparations recorded in the Chinese Pharmacopoeia of 2020 edition were Glycyrrhizae Radix et Rhizoma,Angelicae Sinensis Radix,Poria,Chuanxiong Rhizoma,Scutellariae Radix,Paeoniae Radix Alba,Astragali Radix,Citri Reticulatae Pericarpium,Rehmanniae Radix,Atractylodis Macrocephalae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Borneolum Syntheticum,Platycodonis Radix,Rhei Radix et Rhizoma,Rehmanniae Radix Preparata,Aucklandiae Radix,Carthami Flos,Ophiopogonis Radix,Codonopsis Radix and Angelicae Dahuricae Radix.The results suggest that there were still problems existing in Chinese Pharmacopoeia of the 2020 edition,i.e.,some of the drugs of Chinese patent medicines were not listed in the Chinese medicine material and sliced herbal medicine,and some of the prepared drugs of Chinese patent medicines were not listed in the Chinese medicine material and sliced herbal medicine,either.The systemic analysis of the general information of Chinese medicinal materials as well as their correlation with Chinese patent medicines in Chinese Pharmacopoeia will provide a reference for further research on the production of Chinese medicine material and sliced herbal medicine and the complete list of drugs in Chinese patent medicines.

In order to help the standardized residency training of nuclear medicine residents, the standardized residency training base of nuclear medicine residents in Peking University People's Hospital, combined with forty-five nuclear medicine departments of teaching hospital, established the WeChat official account of "Standardized Residency Training of Nuclear Medicine" and submitted one teaching case per week. The appearance of the WeChat official account of "Standardized Residency Training of Nuclear Medicine" has made up for the shortcomings of insufficient teaching cases in a single training base, strengthened the training of residents' imaging diagnostic thinking, and promoted mutual learning among the bases. By writing teaching cases, instructors and residents have opened up ideas, increased knowledge, improved self-learning ability, and cultivated imaging diagnostic thinking. With the flexible and practical features of the WeChat official account, the consciousness and sustainability of residents' learning have been enhanced.

Objective:To analyze the features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected with other common respiratory pathogens among coronavirus disease 2019 (COVID-19) patients in Shanghai City, and to provide a reference for scientific prevention and control of COVID-19 and other respiratory infectious diseases.Methods:Descriptive epidemiological approaches were used to analyze the data of COVID-19 reported cases in Shanghai City from January 2020 to February 2021 in the information system of Chinese Disease Prevention and Control. Clinical data of the participants were collected, and their SARS-CoV-2 nucleic acid-positive respiratory specimens were collected at the time of illness onset or admission. Multiplex reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect the 22 respiratory pathogens. Independent-samples t test was used for statistical analysis. Results:Of the 272 patients with COVID-19, 15(5.5%) had co-infection of SARS-CoV-2 with other respiratory pathogens, all of which were double infection. There were three cases infected with enterovirus/rhinovirus, two of each with adenovirus, human metapneumovirus and coronavirus NL63/HKU1, and one of each with coronavirus 229E, influenza A virus H1N1, parainfluenza virus 1 and respiratory syncytial virus B. Two cases infected with Mycoplasma pneumoniae. Among the 272 COVID-19 patients, 212(77.9%) had fever, 117(43.0%) had cough, 46(16.9%) had fatigue, and 35(12.9%) had sore throat. The white blood cell count of co-infection cases was higher than that of non-co-infection cases ((6.8±1.7)×10 9/L vs (5.3±1.6)×10 9/L), and the difference was statistically significant ( t=3.09, P=0.008). Conclusions:There is a certain proportion of co-infection of SARS-CoV-2 with other respiratory pathogens among the COVID-19 cases in Shanghai City, mainly viral pathogens, especially enterovirus/rhinovirus. A rational combination of drugs was recommended to improve the cure rate. Surveillance of acute respiratory infection should be further strengthened as well.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.