OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China， providing a reference for promoting enterprise R&D and production， as well as improving the supply guarantee mechanism for pediatric medicines. METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval， Pharnexcloud biomedical database， and National Medical Insurance Drug Directory， this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing. RESULTS As of June 30， 2024， a total of 68 pediatric medicines had been approved through the priority review and approval process， covering 12 therapeutic areas， with oral dosage forms accounting for 64.71%. The median time from application to inclusion in priority review was 35.50 days， with an average of 41.69 days. The median time from inclusion in priority review to market approval was 1.24 years， with an average of 1.42 years. This included 12 domestic new medicines， 21 domestic generic medicines， 35 imported medicines， as well as 29 pediatric-specific medicines and 21 orphan medicines. Additionally， 31 of these medicines had been included in the medical insurance catalog， representing a proportion of 45.59%. CONCLUSIONS Currently， a trend of differentiated competition is emerging between domestic and imported pediatric medicines. The therapeutic areas for pediatric medicines are continuously expanding， and the dosage forms are becoming more tailored to children’s needs. However， there are still issues such as slow progress in new medicine development， insufficient stability in the medicine review and approval process， and a need to increase the proportion of medicines included in medical insurance.

Cationic liposomes,as non-viral vectors,are widely used in gene therapy and gene silencing.Although numerous cationic liposomes have various structures,they can all improve the per-formance of gene delivery.As gene therapy is increasingly studied,it may be foreseen that new cationic lipoplexes will be explored.In this review,we aim to discuss four constituent domains of cationic lipids(headgroup,hydrophobic domain,linker and helper lipids)in gene delivery.This article attempts to demonstrate that various lipid structures show different transfection efficiency and cytotoxicity by sum-marizing the similarities and differences between the four parts of cationic lipids.Furthermore,their major influencing factors are covered.Finally,three clinical cases of ionizable lipids are described to reveal their characteristics and differences from cationic lipids.This paper is intended to provide a conceptual framework for the design of cationic liposomes and for the selection of cationic lipids.

Objective To explore the morphological characteristics of overlapping bloodstains and judge the deposition sequence of bloodstain patterns.Methods The overlapping bloodstains formed by drip stains and bloody shoe prints were simulated on ceramic tiles,and the morphological characteristic differences of 6 group overlapping bloodstain patterns were analyzed to screen effective indicative characteristics.A survey was held to measure the accuracy of the participants in judging the blood deposition sequence without and with information about the morphological characteristic guidance.Results After participants mastered morphological characteristics,the accuracy of judging deposition sequence increased from 59.5%to 89.0%,and the accuracy of judging dry and wet conditions of the primary bloodstains increased from 45.6%to 65.3%.Conclusion According to the morphological characteristics of bloodstains,not only the deposition sequence of bloodstains can be effectively judged,but also the dry and wet conditions of bloodstains can be judged,so as to infer the time interval of bloodstains deposition,which can provide technical support for the analysis and reconstruction of crime scene.

Over the past 30 years,nano-drug delivery systems(NDDS)have become a promising field of drug research.However,a poor knowledge of the in vivo process of NDDS,the limited methods of pharmacokinetic correlation,and the inability to effectively provide strong support for the construction of upstream drug as well as the evaluation of downstream pharmacology and toxicology have become the technical bottleneck for their clinical transformation.Lipid nanodrug(LND)is the most successful NDDS for industrial transformation with great biocompatibility.Taking LND as an example,this paper reviewed the delivery process and influencing factors in vivo,and summarized the regulatory mecha-nism of biological environments on drug release in vivo.Based on advanced spectroscopy and mass spectrometry techniques,the spatial and temporal distribution of the dynamic carrier particle/depolymer-ized molecule ratio and dynamic free/encapsulated drug ratio of LND in biological matrix were ana-lyzed.Finally,the existing problems and future developments in this field were summarized to provide references for the analysis of NDDS in vivo,and stimulate readers'interest in nanomedical research and development.

Non-conventional yeasts such as Yarrowia lipolytica, Pichia pastoris, Kluyveromyces marxianus, Rhodosporidium toruloides and Hansenula polymorpha have proven to be efficient cell factories in producing a variety of natural products due to their wide substrate utilization spectrum, strong tolerance to environmental stresses and other merits. With the development of synthetic biology and gene editing technology, metabolic engineering tools and strategies for non-conventional yeasts are expanding. This review introduces the physiological characteristics, tool development and current application of several representative non-conventional yeasts, and summarizes the metabolic engineering strategies commonly used in the improvement of natural products biosynthesis. We also discuss the strengths and weaknesses of non-conventional yeasts as natural products cell factories at current stage, and prospects future research and development trends.
Yeasts/genetics* ; Yarrowia/metabolism* ; Gene Editing ; Metabolic Engineering

The system of compassionate drug use in China is in the preliminary exploration stage， and the formal management methods and specific implementation rules have not been promulgated， which needs to be further optimized and perfected. Japan realizes the advanced use of unapproved drugs by expanded access clinical trial system， and makes clear provisions on information acquisition， target patient， informed consent， subject of application， implementation plan， handling of refusal to administer medication， drug expenses， implementation deadline， compensation for accidental damages， post-approval data review after expanded access clinical trials. When the enterprise refuses to give drugs because of the “legitimacy reasons of the system”， the attending physician can also apply to the Ministry of Health， Labor and Welfare， and the Ministry of Health， Labor and Welfare will conduct the licensing evaluation to maximize the drug for patients. This “refusal to administer” reprocessing is a unique regulation in Japan， which ensures the accessibility of drugs to the greatest extent possible. Based on the analysis of the expanded access clinical trial system in Japan， it is found that our country could further build the information platform for compassionate drug use， play the leading role of physicians， protect the interests of enterprises， pay attention to the ethical review， and make drug cost payment problems further clear in order to improve and optimize the system of compassionate drug use.

Objective To investigate the microstructural changes in white matter of pituitary adenoma patients when the anterior visual pathway is compressed using diffusion tensor imaging(DTI)and discuss the clinical significance of these changes.Methods Clinical and MRI data of 25 patients with pituitary adenomas and 25 matched healthy controls were prospectively included.Tract-based spatial statistics(TBSS)was carried out to investigate difference in white matter integrity between 2 groups,which was measured using fractional anisotropy(FA).A correlation between visual function evaluation index and regional FA value was examined using correlation analysis.Results The FA values of bilateral optic radiations and inferior fronto-occipital fasciculus were significantly lower in the research group.The FA values of left optic radiation and inferior fronto-occipital fasciculus were positively correlated to mean deviation and visual field index,negatively correlated to patten standard deviation.The FA values of bilateral optic radiations and inferior fronto-occipital fasciculus were negatively correlated with Bulbo-pontine height.Conclusion Patients with pituitary adenoma may experience damage to the bilateral optic radiation and inferior fronto-occipital fasciculus after compression of the anterior visual pathway,which may affect the patient's visual function,further indicating that DTI can quantitatively assess the microstructure damage of the visual pathway in patients with pituitary adenoma.

Objective:To explore the implementation effect and problems of the policy of encouraging generic drug list in China,in order to further improve the policy of generic drug list.Methods:The selection principle of encouraging generic drug list in China,the characteristics and implementation status of included drugs,and the existing problems are analyzed.Results:The therapeutic fields of drugs included in the two batches of catalogs are relatively concentrated in the nervous system,respiratory system,tumor,en-docrine and metabolic diseases and infectious diseases.Among the 50 drugs,there are 24 new applications for generic drugs,2 drugs are included in the priority review,19are approved for listing,and 20 are included in the medical insurance catalog.At present,there are still problems in the development of the two batches of catalogs,such as the ineffective implementation of the second batch of cata-log policies,the phenomenon of"polarization"in the research and development of some generic drugs,the lack of priority review sys-tem,and the coordination and linkage between departments to be strengthened.Conclusion:It is necessary to improve the system de-sign,strengthen the selection management of reference preparations,improve the supporting incentive measures,mobilize the enthusi-asm of enterprises in research and development,dynamically adjust the generic drug catalog,and strengthen the coordination and link-age of departments.

Objective:To investigate the in vitro influence of IL-24 on the functions of CD8 + T cells from patients with non-small cell lung cancer (NSCLC). Methods:Twenty-eight NSCLC patients and 17 healthy individuals were enrolled in this study. Peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage fluid (BALF) were collected to isolate CD8 + T cells. Real-time reverse transcription-PCR was used to detect the expression of IL-24 receptors (IL-20R1, IL-20R2 and IL-22R1) at mRNA level in CD8 + T cells. Changes in the expression of perforin and granzyme B were measured by flow cytometry after stimulating purified CD8 + T cells with different concentrations of recombinant human IL-24 (10 ng/ml and 100 ng/ml). In vitro direct and indirect contact co-culture systems were established for CD8 + T cells and NSCLC cell line (NCI-H1882 cells). CD8 + T cells induced target cell death and expression of IFN-γ and TNF-α in response to IL-24 stimulation were analyzed. Student′s t test or LSD- t test was used for intergroup comparison. Results:The expression of IL-22R1 at mRNA level was not detected in CD8 + T cells. No significant difference in IL-20R1 or IL-20R2 expression at mRNA level in CD8 + T cells was observed between healthy individuals and NSCLC patients, or between non-tumor sites and tumor sites ( P>0.05). Perforin and granzyme B expression was significantly reduced in CD8 + T cells from peripheral bloods and tumor sites of NSCLC patients as compared with those from healthy individuals and non-tumor sites (all P<0.05). Low concentration of IL-24 (10 ng/ml) did not affect perforin or granzyme B expression in CD8 + T cells ( P>0.05), but high concentration of IL-24 (100 ng/ml) significantly enhanced the expression of perforin and granzyme B in CD8 + T cells from NSCLC patients ( P<0.05). In the direct contact co-culture system, increased ratio of dead target cells and up-regulated IFN-γ and TNF-α expression were induced after stimulating CD8 + T cells from tumor sites in NSCLC patients with high concentration of IL-24 (100 ng/ml), but low concentration of IL-24 (10ng/ml) had no significant influence on CD8 + T cell-induced target cell death and cytokine production. In the indirect contact co-culture system, neither target cell death nor cytokine production induced by CD8 + T cells was affected by IL-24 stimulation. Conclusions:High concentration of IL-24 promoted the in vitro cytolytic function of CD8 + T cells from NSCLC patients, but might not influence the in vivo functions of CD8 + T cells.

Objective To analyze the current status and trends of chronic kidney disease (CKD) burden in China from the global perspective, and to provide reference for the prevention and control of CKD in China. Methods The incidence, prevalence, mortality and disability adjusted life year (DALY) rate of China and other regions were retrieved from GBD 2019. Comparative analyses were carried out to reflect the burden of CKD. Results In 2019, the incidence and the prevalence in females were higher than those in males, while the mortality and the DALY rates in females were lower than those in males. There were obvious distinctions in different age groups and people over 65 years old had a higher CKD burden. The burden of CKD mainly came from hypertensive nephropathy and type 2 diabetic nephropathy. From 1990 to 2019, the DALY rate of CKD in China showed an overall upward trend. After eliminating the differences in age composition, the standardized DALY rate of CKD in China was higher than that in Japan, Korea and Ukraine although lower than the global. The main influencing factors of the burden of CKD were metabolic factors. Conclusion The burden of CKD in China is continuously rising. It is still necessary to pay attention to the three-level prevention and control, and focus on the key people groups and high-risk factors to further reduce the burden of CKD in China.