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.

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

Objective:To explore the efficacy and safety of whole-brain low-dose radiotherapy(LDRT)combined with PD-1 inhibitor sin-tilimab and intrathecal pemetrexed(IP)for the treatment of refractory non-small cell lung cancer(NSCLC)with leptomeningeal metastases(LM).Methods:Retrospective analysies were was performed on eight NSCLC patients with LM at the West China Hospital of Sichuan Uni-versity from December 2022 to May 2024.Among the eight patients,there were four were males and four were females,with a median age of 49 years(rangeing,between 34 to 58 years).All patients were treated with whole-brain LDRT combined with immune checkpoint inhibit-or(ICI)and intrathecal chemotherapy regimens,and the therapeutic efficacy was evaluated according to the Response Assessment in Neuro-Oncology(RANO)criteria and the Karnofsky physical status(KPS)score.Adverse reactions were assessed according to the Common Criteria for the Evaluation of Adverse Events(CTCAE version 5.0).Survival analysis was performed using the Kaplan-Meier method.The classification proportion of cerebrospinal fluid subsets before and after treatment was analyzed using by single-cell sequencing,and the differential ana-lysis of gene expression in parallel cells was performed.Results:The best clinical treatment effects in eight patients were were evaluated us-ing the RANO criteria:five patients(62.5%)were evaluated as improved and three(37.5%)as stable.The median KPS score of the eight pa-tients was 30(20-50)before treatment,which was significantly improved to 60(40-90)after treatment(P=0.000 9).The remission rate of neurological symptoms was 100%(8/8)in eight patients.The median neurological progression-free survival(NPFS)was 12 months.The res-ults of single-cell sequencing in CSF of patientss(P1)showed that the proportion of T cells in the patient samples after whole-brain LDRT treatment was significantly higher than that before treatment(6.08%vs.68.87%),and the proportion of tumor cells was significantly lower(12.92%vs.0.6%).The differential analysis of gene expression showed that CCL5 and CXCL13 were significantly upregulated in T cells of CSF after WB-LDRT treatment.Conclusions:The combination of whole-brain LDRT with ICI and IP in the treatment of NSCLC with LM can signific-antly alleviate neurological symptoms,improve quality of life and prolong the NPFS of patients,which is a safe and effective treatment.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Conjugated oligomers,as analogues of conjugated polymers,allow for constructing ultrafine fluorescent nanoparticles with improved sensing sensitivity due to their more precisely defined molecular structure and smaller size.Herein,a new porphyrin-pyridyl conjugated oligomer,i.e.,Zn-TPP-OMe,was designed and synthesized via Sonogashira coupling strategy and a super-small(～2.0 nm)water-soluble fluorescent nanoprobe(Zn-TPP-OMe nanoparticles(NPs))was subsequent obtained by nanoprecipitation method.Due to the addition reaction of chlorine atom to porphyrin ring,the fluorescence intensity of Zn-TPP-OMe NPs at 619-660 nm significantly decreased with increasing HCLO concentration.Meanwhile,Zn-TPP-OMe NPs aggregated obviously after adding HClO,achieving enhanced fluorescence quenching.The fluorescence detection mechanism was verified by transmission electron microscopy(TEM),proton nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS)analyses.The experimental results indicated that the porphyrin-pyridyl conjugated oligomer nanosystem had high sensitivity(LOD=0.005 μmol/L)and excellent selectivity in detection of HClO,and was successfully applied to the sensing of HClO in actual water samples.

Objective To investigate the expression of prolyl 4-hydroxylase β-polypeptide(P4HB)in glioblastoma multiforme(GBM)and its impact on clinical prognosis,as well as on the proliferation and migration of U87 cells.Methods(1)According to the Cancer Genome Atlas(TCGA)database,GTEx database and GEPIA2 database,the difference expression of P4HB in GBM and normal brain tissues were analyzed by R software.(2)A total of 52 patients with GBM who underwent surgical treatment from February 2017 to December 2019 were collected from Department of Neurosurgery,the Second People's Hospital of Guiyang.The normal brain tissues of 10 patients were selected as controls.Immunohistochemical method was used to detect the expression level of P4HB in tumor tissues and normal tissues.The Kaplan-Meier method with the log-rank test was employed for survival analysis.Receiver operating characteristic(ROC)curve was used to analyze the predictive valuable of P4HB expression in survival rate of GBM.Univariate and multivariate Cox regression analysis were used to identify the expression of P4HB and related clinicopathological factors affecting the survival and prognosis of the patients.(3)Human GBM U87 cells were randomly assigned into three groups:control group,NC-siRNA group and P4HB-siRNA group.P4HB expression was interfered with by the transfection of siRNA in P4HB-siRNA group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the content of P4HB mRNA in U87 cells.Cell counting kit-8(CCK-8)and immunofluorescence assay were used to analyze the effects of P4HB on the proliferation of U87 cells.Scratch test was used to analyze the effects of P4HB on cell migration.Results The expression of P4HB was significantly upregulated in GBM tissues compared with normal brain tissues(P<0.05).The γδ T cells(r=-0.227)and follicular helper T cells(r=-0.226)were negatively correlated with the expression of P4HB,while natural killer cell(r=0.417),macrophages(r=0.374),neutrophils(r=0.344),and immature dendritic cells(r=0.263)were positively correlated with the expression of P4HB.Kaplan-Meier survival analysis showed that the progression-free survival and disease-specific survival of GBM patients with high P4HB expression were significantly lower than those with low expression(P<0.05).ROC curve showed that the area under the curve(AUC)of P4HB in predicting overall survival rate of GBM patients was 0.982,and 1-year,3-year,and 5-year survival was 0.655,0.724,0.861,respectively.The immunohistochemistry results suggested that P4HB protein was significantly highly expressed in GBM tumors.Survival analysis indicated that high expression of P4HB was associated with bad prognosis in GBM patients(P<0.05).Multivariate Cox regression analysis indicated that high expression of P4HB and TERT promoter mutations were the independent prognostic risk factors for GBM(P<0.05).Compared with control group and NC-siRNA group,the expression levels of P4HB were decreased significantly after transfected with siRNA in U87 cells of P4HB-siRNA group(P<0.01),and the proliferation ability and the wound healing rate were decreased significantly in P4HB-siRNA group(P<0.001).Conclusions P4HB is significantly highly expressed in GBM,which indicates that the prognosis of patients is poor.Knockout of P4HB could inhibit cellular proliferation and migration of GBM U87 cells.P4HB may be used as the relevant predictive marker and potential therapeutic target in GBM.

Objective To compare the clinical safety and efficacy of CT-guided hook-wire localization of≤10mm pulmonary ground-glass nodule(GGN)via different path ways before video-assisted thoracoscopic surgery(VATS).Methods The clinical data of a total of 128 patients with 10 mm pulmonary GGN,who received CT-guided hook wire localization before VATS at The Third Hospital of Mianyang of China between July 2018 and March 2023,were retrospectively analyzed.According to the puncturing localization path way mode,the patients were divided into vertical puncturing group(n=88)and non-vertical puncturing group(n=40).The number of puncturing times,the time spent for puncturing localization,the success rate of puncture,the operation time of VATS,and puncture-related complications of the two groups were recorded.Results No statistically significant differences in the gender,age,smoking history,GGN location,puncture position,nodule size,density characteristics of GGN,emphysema,and nodules-pleura distance existed between the two groups(all P＞0.05).Compared with non-vertical puncturing group,in vertical puncturing group the number of puncturing times was smaller,the time spent for localization was shorter,the incidence of pneumothorax was lower,and the operation time of VATS was shorter,the differences in all the above indexes between the two groups were statistically significant(all P＜0.05);and the subgroup analysis of patients whose GGN was overlapped with rib shadow obtained the same results.Binary logistic regression analysis revealed that non-vertical puncturing and the number of puncturing times were the independent risk factors for the occurrence of pneumothorax.Conclusion CT-guided hook-wire localization of≤10mm pulmonary GGN before VATS is clinically safe and effective.Under the condition when the lesion can be localized within the range of 2.0cm and the shadow overlapping of GGN with the rib and blood vessel can be effectively avoided,vertical puncturing path way mode should be preferred,which can effectively reduce the incidence of pneumothorax and shorten the operation time of VATS.

ObjectiveTo investigate effect of Maxing Shigantang and supplemented Guominjian decoction on symptoms and levels of inflammatory cytokines in induced sputum of children with cough variant asthma （CVA）. MethodA total of 118 CVA children who were treated in our hospital from January 2020 to January 2021 were enrolled and randomized into the control group and the observation group with the random number table method. Control group received routine western medicine and the observation group was treated by routine western medicine， Maxing Shigantang， and supplemented Guominjian decoction. In the one-month follow-up， the scores of cough and accompanying symptoms， levels of inflammatory cytokines ［interleukin-10 （IL-10）， interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， neutrophil， eosinophil］ in induced sputum， pulmonary function parameters ［forced vital capacity （FVC）， forced expiratory volume in one second （FEV₁）， FEV₁/FVC］， and treatment outcomes were compared between the two groups. Moreover， the frequency of acute asthma attacks during the three-month follow-up was also compared. ResultNo cases dropped out from this study. After treatment， the scores of cough and accompanying symptoms were decreased in both groups （P<0.05） and were lower in observation group than in control group （P<0.05）. After treatment， FVC， FEV₁， and FEV₁/FVC were raised in both groups and were higher in observation group than in control group （P<0.05）. The increase in the level of IL-10 along with the decrease in levels of IL-5， TNF-α， neutrophil， and eosinophil in induced sputum was found in both groups after treatment （P<0.05）， and observation group had higher level of IL-10 and lower levels of IL-5， TNF-α， neutrophil， and eosinophil than the control group （P<0.05）. The effective rate was 86.44% （51/59） in observation group， which was higher than the 69.49% （41/59） in control group （χ²=4.933， P<0.05）. No serious adverse reaction occurred in either group. The frequency of acute asthma attacks during the three-month follow-up was （1.09±0.18） in observation group， which was lower than the （2.83±049） in the control group （P<0.05）. ConclusionRoutine western medicine combined with Maxing Shigantang and supplemented Guominjian decoction can effectively and safely alleviate the airway inflammatory responses， control the clinical symptoms， improve pulmonary function， and reduce the frequency of acute recurrence in the treatment of CVA children.

Objectives: To investigate the current application status and implementation difficulties of extracorporeal cardiopulmonary resuscitation (ECPR) in children with sudden cardiac arrest. Methods: This cross-sectional survey was conducted in 35 hospitals. A Children's ECPR Information Questionnaire on the implementation status of ECPR technology (abbreviated as the questionnaire) was designed, to collect the data of 385 children treated with ECPR in the 35 hospitals. The survey extracted the information about development of ECPR, the maintenance of extracorporeal membrane oxygenation (ECMO) machine, the indication of ECPR, and the difficulties of implementation in China. These ECPR patients were grouped based on their age, the hospital location and level, to compare the survival rates after weaning and discharge. The statistical analysis used Chi-square test and one-way analysis of variance for the comparison between the groups, LSD method for post hoc testing, and Bonferroni method for pairwise comparison. Results: Of the 385 ECPR cases, 224 were males and 161 females. There were 185 (48.1%) survival cases after weaning and 157 (40.8%) after discharge. There were 324 children (84.2%) receiving ECPR for cardiac disease and 27 children (7.0%) for respiratory failure. The primary cause of death in ECPR patients was circulatory failure (82 cases, 35.9%), followed by brain failure (80 cases, 35.0%). The most common place of ECPR was intensive care unit (ICU) (278 cases, 72.2%); ECPR catheters were mostly inserted through incision (327 cases, 84.9%). There were 32 hospitals (91.4%) had established ECMO emergency teams, holding 125 ECMO machines in total. ECMO machines mainly located in ICU (89 pieces, 71.2%), and the majority of hospitals (32 units, 91.4%) did not have pre-charged loops. There were no statistically significant differences in the post-withdrawal and post-discharge survival rates of ECPR patients among different age groups, regions, and hospitals (all P>0.05). The top 5 difficulties in implementing ECPR in non-ICU environments were lack of ECMO machines (16 times), difficulty in placing CPR pipes (15 times), long time intervals between CPR and ECMO transfer (13 times), lack of conventional backup ECMO loops (10 times), and inability of ECMO emergency teams to quickly arrive at the site (5 times). Conclusion: ECPR has been gradually developed in the field of pediatric critical care in China, and needs to be further standardized. ECPR in non-ICU environment remains a challenge.
Child ; Female ; Humans ; Male ; Aftercare ; Cardiopulmonary Resuscitation/methods* ; Cross-Sectional Studies ; Death, Sudden, Cardiac/prevention & control* ; East Asian People ; Heart Arrest/therapy* ; Patient Discharge ; Retrospective Studies ; Surveys and Questionnaires