Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

Crossmodal transfer is the ability to apply the knowledge acquired in one sensory modality to another. Researches on crossmodal transfer investigate how the brain represents information from different sensory modalities, and provide new insights to improve cognitive processing efficiency and reduce repeated learning. To clarify the characteristics and mechanism of crossmodal transfer, this article first introduced the crossmodal transfer effect in different field of research, such as object recognition, category learning, and time perception. After that, the theoretical researches on the representation type of crossmodal transfer were reviewed, mainly including multisensory theory and multisensory mental imagery theory as well as the supportive and opposite findings. The research progresses on the neural mechanism of crossmodal transfer using ERP and fMRI techniques were introduced, mainly including metamodal theory, and multisensory reverse hierarchy theory as well as the supportive and opposite findings. The objective and subjective factors which influenced crossmodal transfer effect were sorted out, in which we suggested that the modality dominance phenomenon supports the metamodal theory, while other factors such as sensory experience, age, setting of learning tasks and stimulus features support theories such as the multisensory hypothesis. Finally, we described the potential applications of the current research findings on crossmodal transfer and pointed out future research questions in this field.

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.

Transcranial electrical stimulation (tES) is a non-invasive neural modulation technique known for its high safety, patient compliance, and portability. It holds promise as a potential non-pharmacological method for analgesia. However, challenges persist in utilizing tES for pain management, including inconsistent research findings and limited understanding of its analgesic mechanisms. Therefore, by summarizing the advances in the analgesic researches employing the 3 primary tES techniques, transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial random noise stimulation (tRNS), we reviewed the analgesic effects on both acute and chronic pain, as well as the neural mechanisms underlying the analgesic effect of each technique. Accumulating evidence suggests that the analgesic effects of tDCS are significant, but studies on analgesic effects of tACS and tRNS remain limited. And the exact mechanisms of pain relief through tES turned out to be not yet well established. Furthermore, we systematically discussed the limitations of analgesia-related studies employing tES techniques across various aspects, involving research design, stimulation protocol formulation, neural response observation, analgesic effect assessment, and safety considerations. To address these limitations and advance clinical translation, we emphasized utilizing promising stimulation techniques and offered practical suggestions for future research endeavors. Specifically, employing numerical simulation of electric field guided by magnetic resonance imaging (MRI) would reduce variability of outcomes due to individual differences in head anatomy. For this purpose, it is advisable to establish standardized head models based on MRI data from the Chinese populations and validate simulated electric field results in tES research to diminish confounding factors concerning anatomy. Meanwhile, novel techniques like multi-site brain stimulation and interferential stimulation (IFS) could broaden the range of stimulation sites in both scope and depth. Multi-site brain stimulation facilitates modulation of entire neural networks, enabling more sophisticated investigations into the complexity of pain. IFS can reach deep brain tissues without invasive surgical procedures, achieving more comprehensive modulation. Regarding neural response observations, establishing a tES-neuroimaging synchronized platform would enable revealing its mechanisms and personalizing protocols based on inter-subject neural response variability detected through recordings. By integrating tES with various neuroimaging techniques, such as functional MRI, electroencephalography (EEG) and magnetoencephalography, into one unified platform, researchers could examine brain activities in baseline before stimulation, dynamic changes in brain activities during stimulation, and sustained brain responses after stimulation. Additionally, collecting finer-grained data on participant characteristics and pain intensity would enhance the sensitivity of future studies. In designing clinical trials to evaluate chronic pain treatments and reporting the results, adopting the six core outcome domain measures recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) could prove beneficial. Lastly, safety considerations can never be overemphasized in future tES studies especially when combining tES with MRI and EEG techniques. These efforts may help to broaden the research scope, reconcile inconsistencies in findings and elucidate the analgesic mechanisms of tES, thus facilitating the development of pragmatic pain management strategies such as combination therapies and home therapies. Ultimately, these suggestions will maximize the clinical application value of tES in pain treatment to achieve pain relief for patients.

Bladder cancer is one of the most prevalent cancers worldwide, with a high rate of recurrence and mortality, which is the ninth most common malignancy globally. Cystoscopy remains the gold standard for clinical bladder cancer diagnosis, but its invasive nature can lead to bacterial infection and inflammation. Urine cytology is a non-invasive and simple diagnostic method, but it has lower sensitivity in detecting low-grade bladder cancer and may yield false negative results. Therefore, identifying ideal diagnostic and prognostic biomarkers is crucial for accurate diagnosis and effective treatment of bladder cancer. Aptamers, characterized as single-stranded DNA or RNA with unique three-dimensional conformations, exhibit the ability to identify various targets, ranging from small molecules to tumor cells. Aptamers, also known as chemical antibodies, are generated by systematic evolution of ligands by exponential enrichment (SELEX) process and can function similarly to traditional antibodies. They hold numerous advantages over antibodies, such as ease of modification, low immunogenicity, and rapid tissue penetration and cell internalization due to their nucleic acid molecule structure. Since their discovery in the 1990s, aptamers have been widely used in biochemical analysis, disease detection, new drug research and other fields. This article provides an overview of aptamer selection and characterization for bladder cancer, discussing the research advancements involving aptamers in diagnosing and treating this disease. It covers aptamers obtained through different SELEX methods, including protein-SELEX, cell-SELEX, tissue-SELEX, and aptamers from other cancer SELEX; the detection in blood samples and urine samples; and application in targeted therapy and immunotherapy for bladder cancer. Currently, several aptamers capable of identifying bladder cancer have been generated, serving as molecular probes that have played a pivotal role in the early detection and treatment of bladder cancer. Bladder cancer perfusion therapy is well-suited for aptamer drug therapy because it does not require internal circulation, making it a suitable clinical indication for aptamer drug development. In addition, bladder cancer can be detected and monitored by collecting urine samples from patients, making it a preferred disease for clinical conversion of aptamers. While aptamers show promise, there is still much room for development compared with antibodies. There are still many clinically applied cancer biomarkers without corresponding aptamers, and more aptamers targeting different biomarkers should be selected and optimized to improve the sensitivity and accuracy for cancer detection and therapy. The field of aptamers urgently needs successful commercial products to promote its development, and home rapid detection/monitoring, imaging and targeted therapy of bladder cancer by infusion may be the breakthrough point for future application of aptamers.

Diabetes mellitus is a complex metabolic disease involving multiple organ systems in the body.In recent years,its global incidence rate has increased year by year.In China,the blood glucose control of patients with diabetes mellitus who receive oral hypogly-cemic agents or insulin treatment remains poor.In the early disease stages,exercise is important to control blood glucose levels.Recently,many studies have found that the occurrence of type 2 diabetes mellitus was related to declining levels of irisin,an exercise-related muscle factor.Furthermore,studies have found that irisin improved insulin resistance,promoted the production of pancreatic isletβcells,and affected the body's glucose and lipid metabolism.In addition,its levels were also implicated in the occurrence of various complications,such as diabetic nephropathy and diabetes-related cardiovascular diseases.This article summarizes and analyzes the role of irisin in the occurrence and development of diabetes mellitus and further describes its impact and mechanism on various diabetic complications.

Digital intraoral scanning is a hot topic in the field of oral digital technology.In recent years,digital intra-oral scanning has gradually become the mainstream technology in orthodontics,prosthodontics,and implant dentistry.The precision of digital intraoral scanning and the accuracy and stitching of data collection are the keys to the success of the impression.However,the operators are less familiar with the intraoral scanning characteristics,imaging process-ing,operator scanning method,oral tissue specificity of the scanned object,and restoration design.Thus far,no unified standard and consensus on digital intraoral scanning technology has been achieved at home or abroad.To deal with the problems encountered in oral scanning and improve the quality of digital scanning,we collected common expert opin-ions and sought to expound the causes of scanning errors and countermeasures by summarizing the existing evidence.We also describe the scanning strategies under different oral impression requirements.The expert consensus is that due to various factors affecting the accuracy of digital intraoral scanning and the reproducibility of scanned images,adopting the correct scanning trajectory can shorten clinical operation time and improve scanning accuracy.The scanning trajec-tories mainly include the E-shaped,segmented,and S-shaped methods.When performing fixed denture restoration,it is recommended to first scan the abutment and adjacent teeth.When performing fixed denture restoration,it is recommend-ed to scan the abutment and adjacent teeth first.Then the cavity in the abutment area is excavated.Lastly,the cavity gap was scanned after completing the abutment preparation.This method not only meets clinical needs but also achieves the most reliable accuracy.When performing full denture restoration in edentulous jaws,setting markers on the mucosal tissue at the bottom of the alveolar ridge,simultaneously capturing images of the vestibular area,using different types of scanning paths such as Z-shaped,S-shaped,buccal-palatal and palatal-buccal pathways,segmented scanning of dental arches,and other strategies can reduce scanning errors and improve image stitching and overlap.For implant restora-tion,when a single crown restoration is supported by implants and a small span upper structure restoration,it is recom-mended to first pre-scan the required dental arch.Then the cavity in the abutment area is excavated.Lastly,scanning the cavity gap after installing the implant scanning rod.When repairing a bone level implant crown,an improved indi-rect scanning method can be used.The scanning process includes three steps:First,the temporary restoration,adjacent teeth,and gingival tissue in the mouth are scanned;second,the entire dental arch is scanned after installing a standard scanning rod on the implant;and third,the temporary restoration outside the mouth is scanned to obtain the three-di-mensional shape of the gingival contour of the implant neck,thereby increasing the stability of soft tissue scanning around the implant and improving scanning restoration.For dental implant fixed bridge repair with missing teeth,the mobility of the mucosa increases the difficulty of scanning,making it difficult for scanners to distinguish scanning rods of the same shape and size,which can easily cause image stacking errors.Higher accuracy of digital implant impres-sions can be achieved by changing the geometric shape of the scanning rods to change the optical curvature radius.The consensus confirms that as the range of scanned dental arches and the number of data concatenations increases,the scanning accuracy decreases accordingly,especially when performing full mouth implant restoration impressions.The difficulty of image stitching processing can easily be increased by the presence of unstable and uneven mucosal mor-phology inside the mouth and the lack of relatively obvious and fixed reference objects,which results in insufficient ac-curacy.When designing restorations of this type,it is advisable to carefully choose digital intraoral scanning methods to obtain model data.It is not recommended to use digital impressions when there are more than five missing teeth.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective:To conduct a nationwide physician survey to better understand clinicians’ disease awareness, treatment patterns, and experience of Waldenstr?m macroglobulinemia (WM) in China.Methods:This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews.Results:The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-na?ve and relapsed/refractory patients (94% for all patients, 95% for treatment-na?ve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions:This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors’ and patients’ understanding of WM is one of the most urgent issues that must be addressed right now.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.