OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

OBJECTIVE To analyze the current status and challenges in importing rare disease drugs in China， providing references for optimizing the import process and improving relevant policies. METHODS Questionnaires and interviews were conducted with stakeholders involved in rare disease drug importation， including government departments， multinational pharmaceutical enterprises， healthcare institutions， and patient organizations. This explored the current situation and challenges encountered by each party. Expert opinions were synthesized to propose improvement suggestions. RESULTS A questionnaire survey of representatives from 25 multinational pharmaceutical companies in the rare disease field revealed that these companies had a strong willingness to import rare disease drugs， with 58.33% of them practicing diverse import models. However， significant challenges hindered this process， including unclear regulations （54.17%）， complex approval procedures （45.83%）， and excessively long approval cycles （41.67%）， negatively impacting their motivation. Meanwhile， interviews with 13 experts from government departments， healthcare institutions， pharmaceutical enterprises， and patient organizations identified deficiencies in policy design， approval processes， sampling inspection costs， and communication efficiency with regulators. Additionally， the drug import model in special medical zones also required improvement. CONCLUSIONS The importation of rare disease drugs in China faces challenges such as incomplete policies， inflexible regulatory mechanisms， and insufficient communication channels. It is recommended to enhance the rare disease definition criteria， optimize import incentive policies， and refine regulatory models， so as to further optimize the import process of rare disease drugs and improve relevant policies.

Lirispirolides A-L (1-12), twelve novel sesquiterpene-monoterpene heterodimers featuring distinctive carbon skeletons, were isolated from the branches and leaves of Chinese tulip tree [Liriodendron chinense (L. chinense)], a rare medicinal and ornamental plant endemic to China. The structural elucidation was accomplished through comprehensive spectroscopic analyses, quantum-chemical calculations, and X-ray crystallography. These heterodimers exhibit a characteristic 2-oxaspiro[4.5]decan-1-one structural motif, biosynthetically formed through intermolecular [4 + 2]-cycloaddition between a germacrane-type sesquiterpene and an ocimene-type monoterpene. The majority of the isolated compounds demonstrated significant anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells by reducing the production of pro-inflammatory mediators, specifically tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Further investigation revealed that the lirispirolides' inhibition of NO release correlated with decreased messenger ribonucleic acid (mRNA) expression of inducible NO synthase (iNOS).
Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Animals ; Mice ; Tumor Necrosis Factor-alpha/genetics* ; Nitric Oxide/immunology* ; Microglia/immunology* ; Molecular Structure ; Liriodendron/chemistry* ; Monoterpenes/isolation & purification* ; Plants, Medicinal/chemistry* ; Cell Line ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; China

Objective To investigate the regulation of SIRT1 on ovarian granulosa cell in women with poor ovarian response.Methods A total of 60 women who underwent IVF/ICSI-ET were included in this study,30 women in poor ovarian response(POR)group and 30 women in normal ovarian response(NOR)group.The granulosa cells in follicular fluid were isolated and purified by density gradient centrifugation.The granulosa cells of POR group were treated with SIRT1 agonist resveratrol(RESV)or inhibitor EX527,respectively,and the control group was granulosa cells treated without drugs.mRNA levels of SIRT1 and key enzymes of steroid hormone synthesis(StAR,CYP19,CYP17)in granulosa cells were detected by qPCR.The levels of SIRT1,steroid hormone synthesis key enzymes protein and apoptosis-related protein(Bcl-2,Caspase-3)in granulosa cells were detected by Western blot.The apoptosis rate of granulosa cells was detected by TUNEL method.Determination of estradiol in granulosa cell culture medium by chemiluminescence.Results The mRNA and protein levels of SIRT1 in granulosa cells in POR group were lower than those in NOR group(P = 0.003,P<0.001).RESV up-regulated SIRT1 mRNA and protein levels(P<0.001),up-regulated mRNA and protein levels of steroid hormone synthesis key enzyme(P<0.05).EX527 down-regulated SIRT1 mRNA and protein levels(P = 0.023,0.001),down-regulated mRNA and protein levels of steroid hormone synthesis key enzymes(P<0.05).After RESV treatment,the apoptosis rate of granulosa cells was decreased(P<0.001),the Bcl-2 protein level was increased(P<0.001),and the Caspase-3 protein level was decreased(P<0.001).After EX527 treatment,the apoptosis rate of granulosa cells was increased(P<0.001),the Bcl-2 protein level was decreased(P = 0.003),and the Caspase-3 protein level was increased(P<0.001).Conclusion The SIRT1 level in granulosa cells of POR women was lower than that of NOR women.RESV up-regulated SIRT1 expression in granulosa cells.SIRT1 inhibited granulosa cell apoptosis,increased the level of steroid hormone synthesis key enzyme,and promoted estradiol synthesis in granulosa cell.Therefore,SIRT1 activators such as RESV may be a therapeutic agent to improve ovarian reactivity and increase the number of oocytes obtained in women with POR.

Objective:To investigate breast ultrasound imaging and pathological characteristics of patients with hereditary breast cancer-ovarian cancer syndrome (HBOC).Methods:A total of 12 patients with HBOC admitted to Shanxi Province Cancer Hospital from January 2012 to 2021 April were retrospectively analyzed. All patients were pathologically diagnosed as invasive breast cancer based on the preoperative puncture or surgical specimens, including 3 patients with double primary cancers of breast and ovary. The clinical, breast ultrasound imaging and pathological data of patients were analyzed.Results:The ultrasound imaging of HBOC usually showed regular morphology in 8 cases, clear border in 9 cases, no burr sign in 10 cases, no calcification in 10 cases, rear echo in 10 cases; the maximum blood flow velocity was (0.21±0.09) m/s, the vascular resistance index was 0.72±0.17, and aspect ratio ≤ 1 in 8 cases. Among 12 cases of HBOS, 9 cases were invasive ductal carcinoma, 3 cases were breast cancer with medullary features; histological grade: 7 cases of grade Ⅱ, 5 cases of grade Ⅲ; molecular classification: Luminal B type in 2 cases, human epithelial receptor 2 (HER2) type in 4 cases, and triple-negative type in 6 cases. The histological types of 3 patients with double primary cancers of breast and ovary were all high-grade serous carcinoma.Conclusions:HBOC is a type of neoplastic disease with a special genetic background. Ultrasound and pathological manifestations have certain characteristics. Sonographers should improve the understanding of the disease and pay attention to the medical history and family history in order to reduce the rate of misdiagnosis and increase the rate of diagnosis.

Objective:To investigate the ultrasound image and pathological features of invasive fibromatosis, and to provide a basis for the diagnosis of invasive fibromatosis.Methods:The clinicopathological data of 22 patients pathologically diagnosed with invasive fibromatosis from January 2016 to March 2019 in Shanxi Provincial Cancer Hospital were retrospectively analyzed. The clinical, ultrasound and pathological data were also summarized.Results:Ultrasound images of invasive fibromatosis showed irregular morphology, unclear boundaries, uneven echo, spot-like or strip-shaped blood flow signals. The coincidence rate of ultrasound diagnosis was 59.1% (13/22), 3 cases were misdiagnosed as fibrous, fat and other sarcomas, 4 cases were misdiagnosed as nerve-derived tumors, 1 case was misdiagnosed as nodular fasciitis, and 1 case was misdiagnosed as gastrointestinal stromal tumor. The pathological characteristics of invasive fibromatosis were more typical, and the positive expression rate of vimentin and β-catenin in immunohistochemistry was 100.0% (22/22); the coincidence rate of preoperative pathological diagnosis of puncture was 78.6% (11/14), 1 case was misdiagnosed as nerve fiber tumor, 1 case was misdiagnosed as low-grade fibromyxoid sarcoma, and 1 case was misdiagnosed as nodular fasciitis.Conclusion:Invasive fibromatosis has a certain specificity in ultrasound and pathological diagnosis, which can be diagnosed and differentially diagnosed according to the ultrasound image and pathological characteristics.

OBJECTIVE：To put forward some suggestions for the implementation of OTC monograph in China. METHODS ： Literature research was used to comprehensively review the concept ，emergence and development ，function of OTC monograph in USA；referring to experience in USA ，the necessity and feasibility of monograph system for OTC registration and evaluation in China were explored ，and some suggestions were put forward to the implementation of OTC monograph in China. RESULTS & CONCLUSIONS：OTC monograph in USA refers to the regulatory standards that should be followed when selling OTC products not included in new drug applications. The monograph originates from the re-evaluation project of the effectiveness of OTC drugs ， which plays a special role in accelerating the drug marketing and promoting product innovation. The OTC monograph system is necessary to help to optimize the OTC registration and evaluation ，but at present ，the conditions to establish and implement OTC monograph are not yet ripe in China. Based on the optimization of resource allocation and infrastructure construction ，national OTC drug management experience ，OTC monograph can play a full part in OTC registration and evaluation ，in terms of carrying out in-depth research ，taking pilot test ，improving risk management system and enhancing drug review resource allocation ability.

Objective To investigate the association between serum level of secretory type Ⅱ phospholipase A2 (sPLA2 Ⅱ a) and carotid intima-media thickness (CIMT) in elderly patients with metabolic syndrome (MS).Methods A total of 124 consecutive MS patients aged over 65 years were enrolled and another 90 elderly non-MS subjects were served as controls.The serum concentration of sPLA2 Ⅱ a was measured by enzyme-linked immunosorbent assay.Blood pressure,blood lipids and blood glucose levels etc.were also measured.The carotid intima-media thickness was examined by color Doppler ultrasonography.Results Serum level of sPLA2 Ⅱ a was significantly higher in elderly MS patients than in control group [(4.41±1.55)μg/L vs.(2.39±0.97)μg/L,P＜ 0.05].Compared with the control group,elderly MS patients showed CIMT was significantly increased [(1.17±0.24) mm vs.(0.89±0.24)mm,P＜0.05].Serum level of sPLA2 Ⅱ a were higher in elderly obesity patients than in normal BMI subjects [(4.76±0.99)μg/L vs.(2.84±0.54)μg/L,P＜0.05].Multiple regression analysis indicated that sPLA2 Ⅱ a level was an independent risk factor for CIMT in elderly MS patients after adjusting for the effects of BMI,IL-6 and high sensitive C-reactive protein (hs CRP) on CIMT(r=0.38,P＜0.01).Conclusions Serum level of sPLA2 Ⅱ a is increased in elderly MS patients and is independently correlated with CIMT,which has a predictive value for atherosclerosis,sPLA2 Ⅱ a may be involved in the process of vascular endothelial injury.

Objective To clarify the possible gene mutations in luteinizing hormone(LH) receptor gene in a boy with LH independent precocious puberty and probe the mechanism the of diseases caused by LH receptor activating mutations. Methods ( 1 ) Describe the clinical manifestations and laboratory data in a 5-year-old boy with LH independent precocious puberty. (2) Peripheral leukocytes were collected from the proband, his parents and other 20 normal puberty developed males. PCR and direct DNA sequence of 11 exons in LH receptors gene were conducted. Results (1) The proband was diagnosed to have LH independent precocious puberty according to the clinical symptoms and the laboratory tests. (2) A germ-line heterozygous point mutation in the 11 exon of LH receptor gene was found in the proband and his mother:c1193 T→C leading to amino acid change with M398T, which causes consecutively an activation of the LH receptor. (3) Other nucleotide changes in the proband and other normal males include c935 A→ G (N312S) and c1065 T→C(same sense mutation). Conclusions (1) A germ-line heterozygous point mutation in the LH receptor gene with M398T leads to consecutively activation of the LH receptor and LH independent precocious puberty. (2) The same point mutation does not have any influence on the puberty development, menstruation and productive functions of the proband's mother. (3) The LH receptor gene has possible polymorphism in the Han ethnic population.