Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.

Objective To explore the risk factors related to afterload mismatch(AM)after transcatheter mitral valve repair(MitraClip).Methods This was a retrospective cohort study.48 patients hospitalized in the Department of Cardiovascular Medicine,the First Affiliated Hospital of Sun Yat-sen University from December 2021 to December 2023,who underwent MitraClip due to severe mitral regurgitation(MR)were included.Preoperative clinical data,laboratory tests,and preoperative and postoperative color Doppler echocardiographic examination results of surgical patients were collected.AM was defined as the left ventricular ejection fraction(LVEF)decreased by 15％or more after surgery compared with the one before(dLVEF≤-15％).Patients were divided into AM group and non-AM group according to whether afterload mismatch occurred.Univariate and multivariate logistic regression were used to analyze the risk factors of postoperative AM.Results Among 48 patients who underwent MitraClip,14 of them(29.2％)developed afterload-mismatched.For those without AM,their overall LVEF was improved after the operation;for patients in both AM group and non-AM group,their overall left ventricular end-diastolic diameter(LVEDd),left ventricular end-diastolic diameter volume index(LVEDVi)was reduced compared with the preoperative ones.Univariate regression analysis showed that C-reactive protein levels(OR 1.98,95％CI 1.02-3.83),platelets(OR 2.22,95％CI 1.08-4.53),systemic immune inflammation index(OR 1.96,95％CI 1.03-3.71)were associated with an increased risk of AM in patients undergoing MitraClip(all P＜0.05),while those with larger right atrial diameter(OR 0.35,95％CI 0.13-0.93)or moderate to severe tricuspid regurgitation(OR 0.19,95％CI 0.05-0.81)were less likely to develop into AM(both P＜0.05),which is still satisfied after adjustment.Conclusions For patients who underwent MitraClip,C-reactive protein levels,platelets and systemic immune inflammation index(SII)are associated with an increased risk of afterload mismatched,while those with larger right atrial diameter or moderate to severe tricuspid regurgitation were less likely to develop into AM.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Objective To measure and compare the lateral posterior tibial slope (LPTS) , medial posterior tibial slope ( MPTS) and tibial torsion angle ( TTA) between the patients of recuiTent patellar dislocation and the heathy people, and to analyze the correlation between LPTS, MPTS and TTA and the risk factors of recuiTent patellar dislocation. Methods A total of 33 patients (44 knees) with recuiTent patellar dislocation in our hospital from July 2019 to June 2021 were selected and listed as the stud)' group. Twenty-three subjects (46 knees) who were suspected iliac vascular and lower limb vascular diseases during the same period were selected and listed as the control group. All the enrolled researchers had fulllength CT scans date of the lower limbs. Three-dimensional models were reconstructed using Mimics 21. 0 software and then imported into 3-matic software. The LPTS, MPTS and TTA were measured and compared between the two groups. Results In the study group, the LPTS, MPTS and TTA were (7. 69} 1. 42) ° , ( 10. 06} 1. 71) ° , ( 36. 42}8. 13 ) ° , respectively while the control group, the LPTS, MPTS and TTA were ( 8. 42 } 1. 65 ) ° , ( 10. 44 } 0. 86 ) ° , ( 25. 77} 3. 90 ) ° , respectively. There were no signiiicant differences in the LPTS, MPTS and TTA between different genders and sides both in the stud)' group and the control group ( P > 0. 0 5 ) . Compared with the control group, the LPTS in the stud)' group was smaller, and the difference was statistically significant (P<0. 0 5 ) . There was no statistically significant difference between the stud)' group and the control group in the MPTS (P>0. 05). Compared with the control group, the TTA in the stud)' group was higher, and the difference was statistically significant (P< 0. 0 5 ) . Compared with the control group, the LPTS and MPTS in the study group were significant asymmetry, and the difference was statistically significant ( P < 0 . 0 5 ). Conclusion The lateral posterior tibial slope of patients with recurrent patellar dislocation is significantly smaller than that in the healthy people, while there is no significant difference in the medial posterior tibial slope; The tibial torsion angle of patients with recurrent patellar dislocation is significantly larger than in the healthy people; The lateral posterior tibial slope and tibial torsion angle have certain correlation with recurrent patellar dislocation, which can conduct the diagnosis of recurrent patellar dislocation.

Objective: To investigate the morphology and immunohistochemical (IHC) expression of pseudostratified ependymal tubules in ovarian mature teratoma (MT). Methods: Five cases of ovarian MT with pseudostratified ependymal tubules were collected from Shenzhen Hospital(Futian) of Guangzhou University of Chinese Medicine and the Eighth Affiliated Hospital of Sun Yat-sen University from March 2019 to March 2022. In addition, 15 cases of ovarian MT with monolayer ependymal epithelium from Shenzhen Hospital (Futian) of Guangzhou University of Chinese medicine and seven cases of immature teratoma (IMT) from Hainan Provincial People's Hospital from March 2019 to March 2022 were collected as control. The morphologic characteristics and immunophenotypes of pseudostratified ependymal tubules, monolayer ependymal epithelium, and primitive neural epithelial tubules were observed and compared by H&E stain and IHC expression pattern of genes related to the differentiation status of neuroepithelium, namely SALL4, Glypican3, nestin, SOX2, Foxj1, and Ki-67. Results: Mean age of the five patients of ovarian MT with pseudostratified ependymal tubules was 26 years (range from 19 to 31 years). Two tumors were located in the left ovary and three in the right. All five cases were excised, and clinical follow-up was available (mean follow-up 1.5 years; range 0.5 to 3 years). No recurrence was noted in any cases. The pseudostratified ependymal tubules of ovarian MT, which were lined with columnar or oval epithelia up to 4-6 layers, were morphologically similar to the primitive neuroepithelial tubules of IMT and different from monolayer ependymal epithelium of ovarian MT. By immunohistochemistry, SALL4 and Glypican3 were negative, Foxj1 was positive and Ki-67 index was lower in the pseudostratified ependymal tubules and the monolayer ependymal epithelium of ovarian MT. However, the primitive neuroepithelial tubules of IMT showed variably expression of SALL4 and Glypican3, were negative for Foxj1 and high Ki-67 index. All the above three groups expressed nestin and SOX2. Conclusions: The pseudostratified ependymal tubules of ovarian MT, which have morphological similarities to the primitive neuroepithelial tubules of IMT, are similar to the monolayer ependymal epithelia of the MT in immunophenotype. IHC assessment of Foxj1 and Ki-67 is helpful to differentiate the pseudostratified ependymal tubules of ovarian MT from the primitive neuroepithelial tubules of IMT.
Female ; Humans ; Young Adult ; Adult ; Nestin ; Ki-67 Antigen ; Immunohistochemistry ; Ovarian Neoplasms/pathology* ; Teratoma/pathology*

Humans ; Pathology, Molecular ; Urinary Bladder Neoplasms/genetics*

On the base of the paradigms of clinical studies on modern moxibustion by identifying the acupoint sensitization, the records of ancient literature in successive dynasties were collected on "identifying the sensitization" of acupoints in acupuncture. In association with acupoint detection of acupuncture recorded in current textbooks, a novel concept, "exerting acupuncture by identifying the acupoint sensitization" is proposed. Acupoint sensitization is the common initial link of effect achieved by both acupuncture and moxibustion. Hence, on the basis of the routine acupoint selection by differentiating syndrome, the state of acupoint must be considerably emphasized in either acupuncture or moxibustion. The clinical curative effect may be improved by selecting the sensitized points and identifying sensitization. This novel mode of diagnosis and treatment focuses on identifying acupoint sensitization by unifying acupuncture with moxibustion and in coincidence with the modern clinical characteristics of either acupuncture or moxibustion.
Acupuncture Points ; Acupuncture Therapy ; Moxibustion

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".
China ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/adverse effects* ; Reference Standards

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.
China ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/adverse effects* ; Pharmacovigilance

In recent years, liver fibrosis has become a hotspot in the field of liver diseases. MicroRNA(miRNA)-mediated Nod-like receptor pyrin domain containing 3(NLRP3) inflammasome activation is pivotal in the pathogenesis of liver fibrosis. The present study mainly discussed the role of miRNA-mediated NLRP3 inflammasome activation in the pathogenesis of liver fibrosis. Different miRNA molecules regulated liver fibrosis by mediating NLRP3 inflammasome activation, including miRNA-350-3 p(miR-350-3 p)/interleukin-6(IL-6)-mediated signal transducer and activator of transcription 3(STAT3)/c-myc signaling pathway, miR-148 a-induced autophagy and apoptosis of hepatic stellate cells via hedgehog signaling pathway, miR-155-mediated NLRP3 inflammasome by the negative feedback of the suppressor of cytokine signaling-1(SOCS-1), miR-181 a-mediated downstream NLRP3 inflammatory pathway activation through mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)/nuclear transcription factor κB(NF-κB) inflammatory pathway, miR-21-promoted expression of NF-κB and NLRP3 of RAW264.7 cells in mice by inhibiting tumor necrosis factor-α inducible protein 3(A20), and miR-20 b-promoted expression of IL-1β and IL-18 by activating NLRP3 signaling pathway. Additionally, the anti-liver fibrosis mechanism of different active components in Chinese medicines(such as Curcumae Rhizoma, Glycyrrhizae Radix et Rhizoma, Aurantii Fructus, Polygoni Cuspidati Rhizoma et Radix, Moutan Cortex, Paeoniae Radix Alba, Epimedii Folium, and Cinnamomi Cortex) was also explored based on the anti-liver fibrosis effect of miRNA-mediated NLRP3 inflammasome activation.
Animals ; Hedgehog Proteins ; Inflammasomes/metabolism* ; Interleukin-6 ; Liver Cirrhosis/metabolism* ; Medicine, Chinese Traditional ; Mice ; MicroRNAs/genetics* ; NF-kappa B/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Proto-Oncogene Proteins c-myc/metabolism* ; Signal Transduction