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.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide （APS） on inhibitor of differentiation1 （ID1） and protein kinase B （Akt） in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625， 1.25， 2.5， 5， 10， 20 mg·L^-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8（CCK-8） method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer， gastric tumor， and stomach cancer were searched against GeneCards， UniProt， DisGeNET， and Online Mendelian Inheritance in Man （OMIM） for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets， and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR， respectively. ResultsCompared with the adjacent normal gastric tissue， the gastric adenocarcinoma tissue showed increased positive expression of ID1 （χ² =81.00， P<0.01）. Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase （PI3K） /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil （0.1 mg·L^-1） and APS （10， 20 mg·L^-1） groups showed decreased cell proliferation， migration， and colony formation. Compared with the control group， 10， 20 mg·L^-1 APS inhibited the proliferation of MGC-803 cells （P<0.01）， with 10 mg·L^-1 APS demonstrating stronger inhibitory effect. In addition， APS at 10， 20 mg·L^-1 inhibited the migration （P<0.01） and colony formation （P<0.05， P<0.01） of MGC-803 cells. Compared with the control group， APS at 10， 20 mg·L^-1 down-regulated the protein levels of ID1 （P<0.01） and Akt （P<0.05） and the mRNA levels of ID1 （P<0.05， P<0.01） and Akt （P<0.05， P<0.01） in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue， which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects， which is expected to provide new therapeutic targets for gastric cancer treatment.

Objective: To analyze the characteristics of injury surveillance cases among the elderly in Ningbo City, Zhejiang Province from 2014 to 2023, so as to provide the basis for formulating targeted injury intervention measures. Methods: Injury surveillance cases aged ≥60 years were collected from seven injury sentinel hospitals in Ningbo City through the Zhejiang Provincial Chronic Disease Surveillance Information Management System from 2014 to 2023. Population distribution, temporal distribution, injury circumstances, and clinical characteristics were described. Results: A total of 67 259 injury surveillance cases among the elderly were reported in Ningbo City from 2014 to 2023, including 32 159 males (47.81%) and 35 100 females (52.19%). The median age was 68.00 (interquartile range, 14.00) years. The three months with a higher number of cases were December (6 271 cases, 9.32%), August (6 226 cases, 9.26%) and October (6 221 cases, 9.25%). The primary causes of injury were falls (25 276 cases, 37.58%), stabs (12 250 cases, 18.21%), and sprains (11 815 cases, 17.57%). The injury occurred mainly in homes (44 975 cases, 66.87%) and streets/urban areas (16 174 cases, 24.05%). The predominant activities at the time of injury were leisure activities (28 801 cases, 42.82%) and household chores (23 647 cases, 35.16%). The proportions of falls as the cause of injury and injuries occurring at home among females and people aged 80 years and above were relatively high. The predominant sites of injury were upper limbs (23 354 cases, 34.72%) and lower limbs (20 343 cases, 30.25%). The predominant nature of injury were soft tissue injuries (43 345 cases, 64.44%) and bone and joint injuries (22 042 cases, 32.77%). Injuries were primarily mild and moderate in severity, with 46 391 cases (68.97%) and 20 205 cases (30.04%), respectively. The proportion of bone and joint injuries, moderate in injuries among females and people aged 80 years and above was relatively high. Conclusions The main causes of injury surveillance cases among the elderly in Ningbo City from 2014 to 2023 were falls and stabs, and the injuries occurred mainly in homes and streets/urban areas. Female and elderly people have a higher risk of injury.

OBJECTIVE: To explore the differences in perioperative clinical and pathological characteristics of patients with different pathological types of prostate cancer undergoing radical prostatectomy, and to analyze the influencing factors that may affect the extraglandular invasion of ductal adenocarcinoma of the prostate. METHODS: Retrospective collection was made of the radical prostatectomy patients who were admitted to Peking University Third Hospital from December 2011 to April 2021. The patients were screened based on inclusion criteria to obtain basic clinical features and postoperative pathological results. According to the pathological results, the patients were divided into ductal adenocarcinoma group (mixed with ductal adenocarcinoma) and acinar adenocarcinoma group, and a 1 ∶1 propensity score matching was performed to compare the differences in clinical characteristics between the two groups. Univariate and multivariate analyses of the factors related to extraglandular invasion were performed in the matched ductal adenocarcinoma groups. RESULTS: A total of 764 patients with prostate cancer were enrolled in this study, of which 62 patients were confirmed to have ductal adenocarcinoma components by postoperative pathology. There was a statistically significant difference in the proportion of the patients with a history of diabetes in baseline characteristics between the two groups before propensity score matching (29.5% vs. 17.7%, P=0.027). A total of 61 patients with simple acinar adenocarcinoma were successfully matched with the patients with ductal adenocarcinoma, and there was no statistically significant difference in baseline characteristics between the two groups after matching (P>0.05). The comparison of perioperative clinical and pathological features showed that International Society of Urology Pathology (ISUP) grade (P=0.003), pT stage (P=0.004), extraglandular invasion rate (P=0.018) and vascular thrombus rate (P=0.019) in ductal adenocarcinoma group were significantly higher than those in simple acinous adenocarcinoma group. Univariate analysis of the influence factors of extraglandular invasion showed that prostate-specific antigen (PSA) level, prostate volume, ISUP grade, seminal vesicle invasion and perineural invasion might be the influencing factors of extraglandular invasion (P < 0.10). Binary Logistic regression analysis showed that perineural invasion was an independent factor of extraglandular invasion (OR=11.78, 95%CI: 1.97-70.56, P=0.007). CONCLUSION Prostatic ductal adenocarcinoma has a worse prognosis than simple acinar adenocarcinoma. Perineural invasion is the influencing factor of extraglandular invasion of ductal adenocarcinoma.
Humans ; Male ; Prostatic Neoplasms/surgery* ; Retrospective Studies ; Prostatectomy ; Neoplasm Invasiveness ; Middle Aged ; Aged ; Carcinoma, Ductal/surgery* ; Propensity Score ; Adenocarcinoma/surgery*

Objective To explore the application value of vesicourethral anastomosis with maximal urethral length preservation(MULP)and bladder neck preservation(BNP)in laparoscopic radical prostatectomy(LRP)or robot-assisted laparoscopic radical prostatectomy(RALP)for high-risk prostate cancer(HRPC)in terms of early urinary continence and oncology.Methods Clinical data of 23 HRPC patients who underwent LRP(including RALP)with MULP and BNP in our hospital during May 2022 and Jan.2024 were retrospectively analyzed.Patients'basic information,surgical parameters,postoperative complications,oncological outcomes and urinary incontinence were collected and analyzed.Results All operations were completed successfully without conversion to open surgery.The operation time was(108±31)min,average blood loss(112±45)mL,hospital stay(5.5±1.5)days,urethral catheterization time(12.6±1.8)days,and no patient received blood transfusion during operation.The urinary continence rates at the time of catheter removal,and at 1,3,and 6 months after surgery were 39.1％,65.2％,73.9％,and 91.3％,respectively.Two patients had positive margins,both of which were at the neurovascular bundle.No patient developed surgery-related complications,urinary obstruction or fistula after surgery.Conclusion Vesicourethral anastomosis with MULP and BNP in LRP for HRPC can effectively improve patients'early urinary continence rate and postoperative quality of life without increasing the oncological risk.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To discuss the effect of fluid resuscitation on the occurrence of ferroptosis in vascular tissue and the structure of vascular cells in the rats with blast injury complicated with hemorrhagic shock,and to clarify its mechanism.Methods:A total of 54 healthy adult SD rats were randomly divided into normal group,blast injury complicated with hemorrhagic shock(model)group,and the fluid resuscitation(treatment)group,and there were 18 rats in each group.Among them,10 rats were randomly selected to observe the surival status and another 8 rats were selected to detect the other indexes.The average survival time(ST),24 h and 72 h survival rates of the rats in various groups were observed;the blood pressure(BP),heart rate(HR),and respiratory rate(RR)of the rats in various groups were observed;the levels of serum creatinine(Scr),blood urea nitrogen(BUN),lactate(LAC),glucose(GLU),iron ions,glutathione(GSH),and malondialdehyde(MDA)and the activities of aspartate aminotransferase(AST),alanine aminotransferase(ALT)and lactate dehydrogenase(LDH)in serum of the rats in various groups were detected;Western blotting method was used to detect the expression levels of ferroptosis marker proteins glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and heme oxygenase 1(HO-1)proteins in superior mesenteric artery tissue of the rats in various groups;the pathomorphology of the superior mesenteric artery of the rats in various groups was observed.Results:All the rats in normal group survived for 72 h,while the longest ST of the rats in model group did not exceed 9 h.Compared with model group,the ST and 24 h survival rate(SR)of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the BP,HR,and RR of the rats in model group were significantly decreased(P＜0.01).Compared with model group,the BP,HR,and RR of the rats in treatment group were significantly increased after fluid resuscitation(P＜0.05).Compared with normal group,the activities of AST and ALT,and the levels of Scr and BUN in serum of the rats in model group were significantly increased(P＜0.01).Compared with model group,the serum levels of LAC and GLU of the rats in treatment group were significantly decreased(P＜0.01).Compared with normal group,the concentration of iron ion,GSH level,MDA level,LDH activity in serum of the rats in model group were significantly increased(P＜0.05);compared with model group,the concentration of iron ion and LDH activity in serum of the rats in treatment group was significantly decreased(P＜0.01).Compared with normal group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in model group were significantly decreased(P＜0.05);compared with model group,the expression levels of GPX4 and SLC7A11 in superior mesenteric artery tissue of the rats in treatment group were significantly increased(P＜0.05).Compared with normal group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in model group was increased(P＜0.01);compared with model group,the expression level of HO-1 protein in superior mesenteric artery tissue of the rats in treatment group was increased(P＜0.01).The microscopic pathology results showed that the cell arrangement in the layers of the superior mesenteric artery tissue of the rats in model group was disordered,the swelling was significant and the thickness was increased;the pathological changes in superior mesenteric artery tissue of the rats in treatment group was alleviated.The ultramicroscopic pathology results showed that the endothelial cell structure of blood vessels of the rats in normal group was intact,and there was no swelling in the subendothelial matrix;the vascular endothelial cell membrane of the rats in model group was damaged,there were cytoplasmic dissolution and fragmentation,and the swelling of the subendothelial matrix was significant;the swelling of the vascular endothelial cells in treatment group was alleviated.Conclusion:Ferroptosis occurs in vascular tissue of the rats with blast injury complicated with hemorrhagic shock,and fluid resuscitation can alleviate the structural damage of the vascular cells by inhibiting the vascular tissue ferroptosis.