The Chinese Pharmacopoeia is the legal technical standard which should be followed during the research, production, use, and administration of drugs. At present, the new edition of the Chinese Pharmacopoeia is planned to be promulgated and implemented. This article summarizes and analyzes the main characteristics and the content of updates and amendments of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅰ), to provide a reference for the correct understanding and accurate implementation the new edition of the pharmacopoeia.

OBJECTIVE To analyze the impact of intergenerational substitution effect of the drugs with the same indication on fund expenditures for national medical insurance for this indication in China， taking national medical insurance negotiated drugs for non-small cell lung cancer （hereinafter referred to as “NSCLC national negotiation drugs”） as an example. METHODS The sales amounts of 15 types of NSCLC national negotiated drugs in secondary and tertiary public hospitals across seven sample provinces from 2017 to 2023 were collected from the Pharmaceutical Drug Database of the China National Pharmaceutical Industry Information Center. A sliding t-test and Mann-Kendall trend test were used to evaluate the trends in sales amounts and DDDs. Taking epidermal growth factor receptor（EGFR）-tyrosine kinase inhibitors （TKIs） and anaplastic lymphoma kinase （ALK）-TKIs as examples， the generational substitution characteristics of these drugs were analyzed. RESULTS The change points of sales amounts and DDDs differed slightly across provinces； the change points of sales amount were mostly concentrated between the first quarter of 2019 and the second quarter of 2020， while those for DDDs were primarily concentrated in the first to second quarters of 2021. In five provinces， i.e. Beijing， Heilongjiang， Jiangsu， Sichuan and Shaanxi， sales amounts showed no significant upward trend after the breakpoints （P＞0.05）， whereas in Guangdong and Hubei， both sales amounts and DDDs continued to rise significantly following the breakpoints （P＜0.05）. Since 2020， the growth in sales amounts of EGFR-TKIs had slowed. After 2021， the sales amounts and DDDs of first- and second-generation EGFR-TKIs declined， while third-generation EGFR-TKIs showed clear substitution effects. The sales amounts of ALK-TKIs continuedto grow. However， the sales amounts and DDDs of first-generation ALK-TKIs had declined year by year， with second-generation ALK-TKIs demonstrating a significant substitution effect on first-generation ones， while third-generation ALK-TKIs had not yet shown a clear substitution trend. CONCLUSIONS With the annual access to and renewal of drugs in national medical insurance negotiations， the overall expenditure trend for NSCLC negotiated drugs comes to a plateau. The intergenerational substitution relationships of drugs with the same indication achieve a relative balance in fund expenditures for negotiated drugs with the same indication. It is recommended that pharmaceutical companies carefully consider their research pipelines， and that medical insurance authorities， during the renewal management process， pay attention to the impact of drug substitution effects on the overall actual expenditure of medical insurance funds for that specific target or the same indication， and scientifically evaluate the extent of price reductions during contract renewals.

Objective: To investigate the impact of childhood traumatic experiences on individual risktaking decisions in early adulthood using functional nearinfrared spectroscopy (fNIRS), so as to provide the reference for clarifying the brain mechanisms underlying the impact of childhood trauma on individual risky decision. Methods: From December 2023 to March 2024, 28 children with childhood trauma experiences (trauma group) and 32 healthy college students (control group) were selected from Jining Medical University by a combination of stratified descent and convenient sampling methods. All subjects participated in the Iowa Game task fNIRS scanning. The brain activation, functional connectivity, graph theory properties (degree centrality, betweenness centrality, and local efficiency), and Receiver Operating Characteristic (ROC) analysis were performed by using preprocessing fNIRS data. Results: Compared with control group, trauma group showed significantly fewer choice times in the inferior deck (Z=-0.88), and showed significantly decreased activation levels in the right frontalpolar (Z=-2.59), as well as showed significant decreased functional connectivity between left dorsolateral prefrontal and in right dorsolateral prefrontal (Z=-3.78), and between left dorsolateral prefrontal cortex and the right frontal pole (Z=-3.68)(P<0.05). The central index of right inferior frontal gyrus in the trauma group was higher than that in the control group, while the central index of left and right dorsolateral frontal lobes was lower than that in the control group (Z=2.13, -2.53, -2.12, P<0.05). The centrality index of the right inferior frontal gyrus in the trauma group was higher than that in the control group (Z=2.47, P<0.05). The local efficiency indicators of the right inferior frontal gyrus, left and right frontal pole in the trauma group were higher than those in the control group (Z=2.51, 2.17, 2.53, P<0.05). The results of the ROC curve analysis showed that the local efficiency achieved the highest area under the curve (AUC=0.68). Conclusions Young adults with childhood trauma experience tend to choose lower loss, and the frontal pole shows a lack of activation in the whole process of risk decision performance. The abnormalities in the brain connectivity and network properties might be the neural basis of excessive defense mechanisms that childhood trauma leads to risky decisions.

AIM: To explore the current status, research hotspots, and trends of global uveitis research to provide a theoretical basis and references for researchers in the field of uveitis, and promote further development in this area.METHODS: Relevant literatures on uveitis were retrieved from the China National Knowledge Infrastructure(CNKI)database, Wanfang database, and Web of Science core collection database since their establishment until 24 August 2023. The country/publishing institutions, research authors, high-frequency keywords, and burst keywords were visual analyzed by using software such as GraphPad Prism 9, CiteSpace 6.2. R2, and VOSviewer.RESULTS: Research teams for uveitis have been formed in various countries globally. The top three countries in terms of publications are the United States of America(7 585 papers), the United Kingdom(2 412 papers)and Germany(1 679 papers). The top three foreign institutions in terms of publications are Harvard University, Oregon Health & Science University, and Moorfields Eye Hospital, while the top three domestic institutions are Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Chongqing Medical University, and Zhongshan Ophthalmic Center, Sun Yat-sen University. The analysis of high-frequency keywords and burst keywords in Chinese and English shows that research hotspots mainly focus on exploring pathogenesis and different treatment methods for uveitis. The research hotspots related to uveitis treatment are transitioning to molecular biology-related research topics, such as molecular biological signaling pathways(NF-κB signaling pathway with a strength value of 22.89), biological agents(adalimumab with a strength value of 32.21), and tumor necrosis factor(with a strength value of 48.44). Related research is also expanding to basic experiments on relevant rats.CONCLUSIONS: In recent years, the research hotspots and trends of global uveitis mainly focus on precise diagnosis, pathogenesis, and more effective treatment methods. It is important for more scholars to dedicate themselves to uveitis-related research in the future to make breakthroughs and progress in the field. More large-scale and multicenter clinical studies on uveitis can provide high-quality research evidence.

Cervical cancer is a common gynecological malignant tumor. Vaccination with human papilloma virus （HPV） vaccine is of great significance to prevent condyloma acuminatum， HPV infection， and cervical cancer. This paper reviews the epidemic situation and risk factors of cervical cancer， the prevention strategies of cervical cancer， HPV types， HPV vaccine types and mechanisms of action， the safety and effectiveness of vaccines， men’s HPV vaccination， vaccination policies in various countries and so on， and further puts forward suggestions on HPV vaccination policies in China.

BACKGROUND:Gold nanoparticles are of great significance in the development of multifunctional transdermal drug delivery systems.Smaller gold nanoparticles can penetrate the dermis through the intercellular pathway,but are limited to their easy agglomeration and colloidal morphology,which makes it difficult to exert effects on low delivery efficiency. OBJECTIVE:To develop an ultrasound-optimized hydrogel delivery system by combining phase change nanodroplets with bio-adhesive hydrogel for percutaneous delivery of gold nanoparticles. METHODS:The ultrasound-responsive nanodroplets loaded with gold nanoparticles were prepared by the emulsion solvent evaporation method and loaded into the polydopamine-modified methylacryloyl gelatin hydrogel to prepare a composite hydrogel scaffold.The structure and chemical composition of the ultrasound-responsive nanogold carrier were characterized.The microstructure,porosity,permeability,rheology,in vitro hemostasis,and antibacterial properties of the composite hydrogel were characterized.The cell compatibility of the hydrogel scaffold was evaluated by live/dead staining,and the optimization effects of low-intensity pulsed ultrasound on the permeability,porosity,and mechanical properties of hydrogel were evaluated. RESULTS AND CONCLUSION:(1)Transmission electron microscopy and ultraviolet-visible spectroscopy proved the successful construction of nanogold carriers.The particle size and potential results demonstrated that the synthesized nanoscaled ultrasonic responsive carrier had good stability.(2)Live/dead cell staining proved that the prepared composite hydrogel scaffold had certain biocompatibility.(3)Scanning electron microscopy exhibited that the prepared composite hydrogel scaffold had a porous network structure,and numerous pores of about 2 μm appeared inside the macropores after the addition of nanodroplets and ultrasonic irradiation.The permeability experiment displayed that low-intensity pulsed ultrasound could optimize the porosity and permeability of hydrogel materials.The hemostatic performance of the composite hydrogel scaffold was better than that of the hemostatic sponge and polydopamine@methylacrylylated gelatin hydrogel scaffold.Under the irradiation of low-intensity pulsed ultrasound,the composite hydrogel scaffolds had good antioxidant effects and antibacterial properties.(4)Thermal imaging results manifested that gold nanoparticles were encapsulated in ultrasound-responsive nanobubbles,and more uniform dispersion could be obtained under ultrasonic excitation.(5)The results of the mechanical property test demonstrated that the storage modulus of the hydrogel increased before and after loading gold nanoparticles-nanodroplets,which showed stronger mechanical properties.The elongation at break was 122%,and the ductility was better than that without gold nanoparticles-nanodroplets(P<0.05).(6)These findings indicate that the composite hydrogel scaffold has good biocompatibility,antibacterial property,oxidation resistance,and hemostatic effect.

The transgender children and adolescents(TCAs)face serious social dilemmas in the process of gender identity and expression,which hinders this group from seeking reasonable and equal rights to survival and development.From the perspective of equal rights and the theoretical framework of social dilemma,by interviewing TCAs who seek help from medical social workers in a hospital's multi-disciplinary transgender clinic,this paper revealed that under the traditional system of"binary gender",TCAs lacked social inclusiveness and infrastructure,which led to the two major social dilemmas of"social traps"and"social barriers"encountered by this group in the process of gender expression and gender identity.Specifically,the social gender selection of TCAs often leads to collective irrational reactions and gender punishment,preventing their legal and effective medical services.To this end,the research team used critical methodology to construct a joint disciplinary diagnosis and treatment path for TCAs with the participation of medical social workers,as well as verified that the path has significant intervention effects in rationalizing the needs of TCAs and their families,alleviating their psychological pressure and social adaptation problems in the process of gender identity,fostering a diverse dialogue environment in their families,as well as enhancing their self-efficacy and social participation,to provide assistahce to the TCAs groups in social difficulties,assisting their rights and interests be included in the child-friendly indicator system,and improving the whole society's tolerance and understanding for TCAs group.

The disease risk prediction model is the basis of precision prevention and an essential reference for clinical treatment decisions. The development of risk prediction models requires the support of a large amount of high-quality data. A large population cohort study is an important basis for this study. The United Kingdom Biobank (UKB), as a mega-population cohort and biobank, has played an essential role in the exploration of disease etiology and research related to disease prevention and control, with its rich baseline and follow-up data and concepts and mechanisms shared globally. This study followed PRISMA guidelines and included 210 articles with corresponding authors from 18 countries, of which 58 (27.62%) were from the UKB. A total of 491 disease risk prediction models were extracted for cancer, cardiovascular and cerebrovascular diseases, endocrine and metabolic diseases, respiratory diseases, and other diseases and their subgroups, of which 132 were developed by UKB without validation, 183 were developed by UKB with internal validation, 17 were developed by UKB with external validation, and 159 were developed by external development with UKB validation. A total of 188 models used only macro variables (38.29%), and 303 models combined macro and micro variables (61.71%). Model construction methods included survival outcome models, logistic regression, and machine learning. Survival outcome models were dominated by Cox proportional risk regression models and a few models considering competitive risk, accelerated failure models, or different baseline risk functions. Machine learning models included random forest, XGBoost, CatBoost, support vector machine, convolutional neural network, and other methods. The UKB is an essential resource for multiple disease risk prediction modeling studies.

Objective:To analyze regional differences in MMACHC gene variations among patients with cblC-type methylmalonic acidemia (MMA) in China and to explore the relationship between these variations and neonatal screening, biochemical markers and prognosis.Methods:Retrospective case summary. Clinical and laboratory data, including general condition, biochemical markers and genetic analysis, were collected from 1 859 cblC MMA patients from 2005 to 2023. Patients were divided into 7 groups according to their regions: north China, northeast China, east China, central China, south China, southwest China and northwest China. They were also classified into neonatal screening and non-neonatal screening groups. Mann-Whitney U and Kruskal-Wallis tests were used to compare biochemical marker levels. In contrast, the Chi-square test was applied to compare MMACHC gene variant frequencies, neonatal screening proportion, onset age and prognosis between groups. Results:Among 1 859 cases of cblC MMA, 1 019 were male and 840 were female, with a consultation age of 1.0 (0.1, 5.0) month. A total of 1 787 cases carried compound heterozygous or homozygous variants and only 1 variant site was identified in 72 cases. The 10 most frequent variants were c.609G>A (1 238 cases), c.658_660delAAG (343 cases), c.80A>G (284 cases), c.482G>A (239 cases), c.567dupT (191 cases), c.656_658delAGA (131 cases), c.217C>T (109 cases), c.394C>T (105 cases), c.445_446delTG (51 cases) and c.1A>G (50 cases). The frequency of the c.609G>A was the lowest in northwest China (28.8% (44/154), χ2=-18.42, P<0.05). The frequency of the c.567dupT was the most common in southwest China (25.0% (20/80), χ2=71.70, P<0.001) and c.656_658delAGA had the highest frequency in northeast China (9.3% (19/205), χ2=32.08, P<0.001). Non-missense variants (91.2% (62/68), 88.5% (46/52)) and early-onset patients (90.0% (36/40), 94.4% (34/36)) were both more prevalent in southwest and south China ( χ2=14.95, 31.69, both P<0.05). The proportion of neonatal screening was the lowest in south China (22.2% (8/36), χ2=98.48, P<0.05), where the mortality rate was the highest (19.1% (4/21), χ2=38.98, P<0.001). East China exhibited the highest frequency of missense variants (21.5% (339/1 579)), the highest proportion of patients identified through neonatal screening (54.5% (465/853)), and a more significant proportion of patients with good prognosis (36.6% (227/621), χ2=14.57, 93.49, 38.98, all P<0.05). In addition, the c.482G>A variant was more frequent in patients diagnosed by neonatal screening compared to those diagnosed by other methods (8.3% (132/1 586) vs. 5.9% (122/2 060), χ2=7.97, P<0.05). Conclusions:The frequency of MMACHC gene variation varies across different regions. The c.609G>A was least frequent in northwest China, c.567dupT was most common in southwest China, and c.656_658delAGA was most prevalent in northeast China. South China had the lowest neonatal screening rate and the highest mortality. At the same time, east China exhibited the highest frequency of missense variants, the highest proportion of patients identified through neonatal screening and the best prognosis. The c.482G>A variant was more frequent in patients diagnosed by neonatal screening compared to those diagnosed by other methods.

CLDN6 is a member of the CLDNs family that is specifically and highly expressed in cancers such as ovarian, testicular, endocervical, liver and lung adenocarcinoma, but hardly expressed in adult normal tissues. CLDN6 is able to activate multiple signaling pathways, which take part in the development and progression of cancer, including promoting tumor growth, migration and invasion, and promoting chemoresistance in cancer. In recent years, CLDN6 has received much attention as a novel target for cancer therapeutics. Many types of anticancer drugs targeting CLDN6 have been developed, including antibody-conjugated drugs (ADC), monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T-cell immunotherapy (CAR-T). This paper briefly summarizes the structure, expression and function of CLDN6 in tumors, and reviews the current status and ideas of developing targeted CLDN6 anticancer drugs.
Signal Transduction ; Immunotherapy ; Antibodies, Monoclonal ; Neoplasms/drug therapy*