OBJECTIVE To provide references and recommendations for improving the regulatory framework for cell and gene therapy products and treatments in China. METHODS This study systematically examined the “dual-track regulatory” frameworks for regenerative medicine products and treatments in Japan and the Republic of Korea， summarized their beneficial experiences， and explored optimization strategies for China’s regulatory practices. RESULTS & CONCLUSIONS Both Japan and the Republic of Korea have established clear management processes for two distinct pathways “registered clinical trials for regenerative medicine products” and “clinical research on regenerative medicine treatments” guided by shared principles of “risk stratification” and “full lifecycle oversight”. Based on these findings， it is recommended that China： strengthen top-tier legislative framework to explicitly delineate the regulatory scope governing cell and gene therapy products and treatments； clarify the jurisdictional responsibilities of relevant regulatory bodies to enhance oversight efficacy； appropriately calibrate the regulatory scope， and adopt a balanced regulatory approach that harmonizes standardization with innovation incentives， thereby accelerating the clinical translation of regenerative medicine products.

Vasovagal syncope is the common type of unexplained syncope,and non-drug therapy is the primary method for its treatment.Till now,there are obvious limitations of western medicine treatment.Vasovagal syncope can be attributed to the category of"syncope syndrome"in the field of traditional Chinese medicine.Professor Wu Wei believes that the fundamental pathogenesis of vasovagal syncope is due to the failure of spleen yang in ascending,and the therapeutic method is to elevate and flourish spleen yang.Professor Wu established the basic formula for elevating spleen yang,which is maily composed of Astragali Radix,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,Fici Simplicissimae Radix,Citri Reticulatae Pericarpium,Bupleuri Radix,salt-prepared Eucommiae Cortex,wine-prepared Corni Fructus,Psoraleae Fructus,Aconiti Lateralis Radix Preparata,Paeoniae Radix Alba and Zingiberis Rhizoma Recens.The formula has the primary actions of elevating and flourishing spleen yang,and also has the auxiliary effect on nourishing heart,soothing liver and warming kidney.The treatment of vasovagal syncope using the method of elevating and flourishing spleen yang by Professor Wu Wei has achieved satisfactory efficacy,and his experience can provide a reference for the clinical treatment of vasovagal syncope with Chinese medicine.

ObjectiveTo explore the compliance related factors of repeated screening for colorectal cancer in Jiading District， and to provide a scientific basis for the prevention and control of colorectal cancer. MethodsBased on the natural population cohort in Jiading District， and the screening situation in 2017‒2019 and 2020‒2022， the study subjects were divided into the groups of never participating in screening and participating in screening. Subjects in the participating group were further divided into participating in one round of screening or having repeated screening. SPSS 21.0 software was used to analyze the demographic characteristics of each group. χ² test or Fisher precise probability test were used to conduct univariate analysis of the factors such as gender， age， education level， marital status， retirement status， and type of medical insurance. Factors with the significant difference （P<0.05） were selected for inclusion in multivariate analysis， and factors related to compliance with repeated screening were analyzed by multivariate logistic regression. ResultsA total of 8 179 subjects were included in the study， including 3 323 males （40.6%） and 4 856 females （59.4%）. The average age of the subjects was （61.26±6.06） years old. A total of2 652 （32.4%） had educated in primary school or below， 4 242 （51.9%） in secondary school， and 1 285 （15.7%） in higher secondary school. Mostly， 7 579 （92.7%） were married. Among the participants， 4 062 people had never participated in screening， 4 117 people had participated in screening， and 1 485 of them had repeated screening， with a repeated screening rate of 18.2%. Multivariate logistic regression analysis showed that women had better compliance with repeated screening than men （OR=1.31， 95%CI： 1.14‒1.50）. Compared with the population aged 50 to 54 years， the population aged 55‒59 years （OR=1.57， 95%CI： 1.19‒2.08）， 60-64 years （OR=2.77， 95%CI： 2.13‒3.61）， and 65-69 years （OR=3.31， 95%CI： 2.51‒4.36） had higher compliance with repeated screening. Compared with employees' medical insurance， residents' medical insurance group had worse compliance with repeated screening （OR=0.76， 95%CI： 0.66‒0.87）. People with a history of intestinal polyps were more likely to undergo repeat screening than those without （OR=2.07， 95%CI： 1.50‒2.87）. ConclusionCompliance with repeated screening for colorectal cancer still needs to be improved， and there are differences in compliance with repeated screening for different populations with different characteristics. Identifying groups that are unlikely to adhere to community-based colorectal cancer screening and taking targeted interventions can help improve the continued compliance of residents with colorectal cancer screening.

Stress urinary incontinence (SUI) and underactive bladder (UAB) are common types of lower urinary tract dysfunction in women.As the treatment mechanisms of the two conditions are contradictory, the treatment of SUI patients complicated with UAB remains a difficult clinical problem.In order to improve the treatment rate of such patients and promote research, this paper reviews the latest domestic and overseas diagnostic criteria of UAB, summarizes the treatment experience of conventional midurethral sling (tension-free vaginal tape or outside-in transobturator tape) and adjustable sling procedures (transobturator adjustable tape or Remeex system) combined with medication or intermittent catheterization, and the application prospects of cutting-edge technologies such as stem cell injection, cytokine therapy and gene therapy, so as to provide reference for clinicians and researchers.

The pricing and reimbursement of orphan drugs are related to the accessibility of patients,and are of great significance to the prevention and guarantee of rare diseases.European countries have formed special standards and paths for health technology evaluation,and established special payment funds and diversified risk-sharing agreements,which have effectively improved the accessibility of orphan drugs.Based on this,it selected typical European countries to compare the orphan drug pricing and reimbursement methods.Then,it put forward some suggestions"building orphan drug health technology evaluation accelerated program,exploring the health of orphan drug classification security mechanism,and attaining supply incentives and development incentives through orphan drug pricing and adjustment",to optimize the basis for the orphan drug market access mechanism to provide reference.

Myeloid neoplasms (MNs) belong to a group of hematological malignancies characterized by the abnormal biological functions of hematopoietic stem progenitor cells. The abnormal immune and hematopoietic microenvironment of patients with MN interact with malignant clonal hematopoietic stem cells, promoting the occurrence and development of their diseases. MN large granular lymphocyte proliferation (MN-LGLP) is a special and rare clinical phenomenon in this type of disease. Currently, research on this disease in domestic and international cohorts is limited. This study analyzes the clinical and laboratory characteristics of this type of patient and explores the impact of LGLP on the clinical characteristics and survival of patients with MN. Patients with MN-LGLP are prone to neutropenia and splenomegaly. The presence of LGLP is not a risk factor affecting the survival of patients with MN-LGLP. STAG, ASXL1, and TET2 are the most common accompanying gene mutations in MN-LGLP, and patients with MN-LGLP and STAG2 mutations have poor prognoses.

Interleukin-1 receptor-related kinase (IRAK4) is a widely expressed serine/threonine kinase involved in the regulation of innate immunity. IRAK4 plays a pivotal role as a key kinase within the downstream signaling pathway cascades of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs). The signaling pathways orchestrated by IRAK4 are integral to inflammatory responses, and its overexpression is implicated in the pathogenesis of inflammatory diseases, autoimmune disorders, and cancer. Consequently, targeting IRAK4-mediated signaling pathways has emerged as a promising therapeutic strategy. Small molecule inhibitors and degraders designed to modulate IRAK4 have shown efficacy in mitigating related diseases. In this paper, we will provide a detailed description of the structure and function of IRAK4, the role of IRAK4 in related diseases, as well as the currently reported small molecule inhibitors and degraders of IRAK4. It is expected to provide new directions for enriching the clinical treatment of inflammation and related diseases.

Although the development of COVID-19 vaccines has been a remarkable success, the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict. In this study, blood samples were collected from 163 participants who next received two doses of an inactivated COVID-19 vaccine (CoronaVac®) at a 28-day interval. Using TMT-based proteomics, we identified 1,715 serum and 7,342 peripheral blood mononuclear cells (PBMCs) proteins. We proposed two sets of potential biomarkers (seven from serum, five from PBMCs) at baseline using machine learning, and predicted the individual seropositivity 57 days after vaccination (AUC = 0.87). Based on the four PBMC's potential biomarkers, we predicted the antibody persistence until 180 days after vaccination (AUC = 0.79). Our data highlighted characteristic hematological host responses, including altered lymphocyte migration regulation, neutrophil degranulation, and humoral immune response. This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after COVID-19 vaccination, shedding light on immunization mechanisms and individual booster shot planning.
Humans ; COVID-19 Vaccines ; Leukocytes, Mononuclear ; Proteomics ; COVID-19/prevention & control* ; Vaccination ; Antibodies ; Antibodies, Viral ; Antibodies, Neutralizing

OBJECTIVE To systematically introduce the supply guarantee system of orphan drugs in South Korea， and to provide reference for improving the accessibility of orphan drugs in China. METHODS The basic characteristics and practical experience of supply guarantee system of orphan drugs in South Korea were summarized by studying the marketing incentive mechanism， reserve supply mechanism and emergency use mechanism. Then， based on the research on the current situation and existing problems of orphan drug supply in China， specific suggestions were put forward to improve the accessibility of orphan drugs in China. RESULTS & CONCLUSIONS South Korea has effectively improved the accessibility of orphan drugs through orphan drug identification channels and supporting incentive policies， relying on the reserve supply mechanism and the import route for emergency use. Therefore， it is suggested that China should guarantee the normal supply of orphan drugs from three aspects： improving the recognition and incentive policy of orphan drugs， building a full-time management department of orphan drugs， and optimizing the temporary import path.

Diabetic nephropathy(DN)is a common complication of diabetes and a leading cause of end-stage renal disease.Transforming growth factor-β1(TGF-β1)/SMAD signaling activation plays an important role in the onset and progression of DN.Reported findings suggest that the activation of TGF-β1(including the latent form,the active form,and the receptors)and its downstream signaling proteins(SMAD3,SMAD7,etc.)plays a critical role in DN.In addition,TGF-β1/SMAD signaling may mediate the pathogenesis and progression of DN via various microRNAs(miRNAs)and long non-coding RNAs(lncRNAs).Emerging evidence shows that TGF-β1,SMAD3,and SMAD7 are the main signaling proteins that contribute to the development of DN,and that they can be potential targets for the treatment of DN.However,recent clinical trials have shown that the anti-TGF-β1 monoclonal antibody treatment fails to effectively alleviate DN,which suggests that upstream inhibition of TGF-β1/SMAD signaling does not alleviate clinical symptoms and that this may be related to the fact that TGF-β1/SMAD has multiple biological effects.Targeted inhibition of the downstream TGF-β1 signaling(e.g.,SMAD3 and SMAD7)may be an effective approach to attenuate DN.This article discussed the current understanding of the molecular mechanisms and potential targets for the treatment and prevention of DN by focusing on TGF-β1/SMAD signaling.