The expanded clinical trial system is designed to provide clinical trial drugs for patients suffering from serious or life-threatening diseases for which there is no effective treatment， essentially seeking a balance between the accessibility of drugs to patients and the soundness of the development of the pharmaceutical industry， as well as between the risk of expanding the use of clinical trial drugs and the need to safeguard the rights and interests of patients’ lives and health. Article 23 of China's Drug Administration Law provides only a principled description of the applicable standards and operating procedures for this system， with no implementing regulations， making it difficult for the system to function effectively in practice. The United States， Japan， and Canada have made detailed provisions on the conditions of application， applicants， review subjects and contents， and safeguards of the system through laws， regulations， and guidelines. Based on China's legislative environment and regulatory reality， and considering that the system is still in the initial stage in China， it is recommended that appropriate reference be made to the beneficial experience of foreign countries and that regulations and normative documents be promulgated as soon as possible to clarify the types of expanded clinical trials， applicants， review subjects etc.， and to determine the responsibilities of all the parties involved， to promote the standardization of China’s expanded clinical trial system， to promote the availability of medicines to patients， and to effectively safeguard the rights and interests of patients’ lives and health， and the soundness and safety of the development of the pharmaceutical industry.

Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury. After injury, Schwann cells produce an inflammatory response and secrete various chemokines, inflammatory factors, and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages, enhancing their phagocytotic ability, and thus play an important role in promoting nerve regeneration. Macrophages have also been found to promote vascular regeneration after injury, promote the migration and proliferation of Schwann cells along blood vessels, and facilitate myelination and axon regeneration. Therefore, there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration, but this has not been systematically summarized. In this review, the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other, to provide directions for research on accelerating nerve injury repair.
Schwann Cells/metabolism* ; Peripheral Nerve Injuries/physiopathology* ; Animals ; Macrophages/immunology* ; Nerve Regeneration/physiology* ; Humans ; Cell Movement/physiology*

Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children.However,certain factors influencing local chickenpox outbreaks have not been studied.Here,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing regions.We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living environment.Furthermore,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease transmission.These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.

Objective:To characterize the antimicrobial resistance, resistance machanism and population genetics of Salmonella( S.) Derby in China, preliminarily reveal the population genetic characteristics of S. Derby in China, discover possible transmission patterns or potential transmission pathways, and provide certain reference for strengthening S. disease monitoring and developing prevention and control strategies. Methods:A total of 201 strains of S. Derby from different areas in China were used for the susceptible tests to 16 antibiotics and whole-genome sequencing. Finally, combined with the genome sequences of 134 strains of S. Derby from public databases, 335 strains of S. Derby were used for resistance genotype analysis and multi-locus sequence typing (MLST), and a phylogenetic tree based on the core genome single nucleotide polymorphisms was constructed for evolutionary analysis. Results:The results showed that 201 strains of S. Derby showed resistance to 16 kinds of antibiotics at different levels. The overall resistance rate was 97.51%. The resistance rates to antibiotics varied in S. Derby from different sources (human, animal, and food), the differences were significant (all P<0.05). A total of 38 resistance genes were carried by 335 strains of S. Derby, of which, fosfomycin gene fosA7 was found in all the strains (100.00%) and aminoglycoside genes aac(6')-Iaa accounted for 99.70%. The consistency of resistance genes and phenotypes varied with antibiotics. Except aminoglycosides and chloramphenicol, the consistencies of resistance genes and phenotypes for other antibiotics were high. MLST showed that 334 strains of S. Derby belonged to ST40. Phylogenetic trees indicated the risk for cross-infection between animal and human, food and human, and the possibility of long-distance interprovincial transmission of the bacteria by animal, to which further epidemiological studies are needed. Conclusions:The drug resistance of S. Derby is serious in China and the risk for cross-transmission between human and animal or food exists. It is necessary to establish and strengthen the comprehensive surveillance and risk assessment to prevent the spread of antibiotic resistant strains or elements through animal, food and human chains.

Objective:To establish a matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) assay for the identification of common Salmonella serotypes and provide etiology evidence for the early precise treatment of salmonellosis. Methods:A total of 500 strains were collected from different regions and sources and five predominant Salmonella serotypes ( Salmonella Typhi , Salmonella Paratyphi A , Salmonella Typhimurium , Salmonella Enteritidis , and Salmonella Indiana) of each strain was identified by agglutination test and whole-genome sequencing. The protein complex of the strains was extracted by using optimized pretreatment method to establish the fingerprint database of peptides for each Salmonella serotype. The new serotyping assays were established by using different modules based on the mass spectra database. Additional 155 strains with specified serotypes and variant sources were used to test and evaluate the accuracy of the new typing assays. Results:Five MALDI-TOF MS databases were established, and two new serotyping assays were established via peptide fingerprint mapping/matching and machine learning of the neuronal convolutional network respectively based on the databases. The results showed that the fingerprint matching approach could quickly identify five common Salmonella serotypes in clinical practice compared with the machine learning method, the accuracy of fingerprint matching assay to identify five Salmonella serotypes reached 100.00% and the serotyping can be conducted within a short time (15-20 minutes) and had a good reproducibility, while the machine learning method could not completely identify these serotypes. Moreover the sensitivity and specificity of fingerprint matching assay were all 100.00% respectively, while they were only 82.23% and 95.81% for machine learning method. Conclusion:The established Salmonella serotyping assay based on MALDI-TOF MS in this study can easily, rapidly and accurately identify different serotypes of Salmonella.

Purpose To observe the changes in the brain microstructure of children with global developmental delay(GDD)via MR diffusion kurtosis imaging(DKI).Materials and Methods A total of 34 children with GDD were included as the experimental group,and 34 children with normal development as the control group in the Third Affiliated Hospital of Zhengzhou University from September 2020 to March 2023,retrospectively.DKI and clinical data were collected.After post-processing,DKI parameters were obtained,including fraction anisotropy,mean kurtosis(MK),axial kurtosis and radial kurtosis(Kr).The differences in parameters in each region of interest of the two groups were analyzed,the correlation between DKI parameters and Gesell developmental scale was analyzed,and the receiver operating characteristic curve was drawn to analyze the diagnostic efficacy of DKI parameters.Results Compared with the control group,the MK value of the centrum semiovale decreased(Z=-2.723,P<0.01),the MK value and Kr value of the thalamus decreased(t/Z=-3.220,-3.128,both P<0.01),the MK value and axial kurtosis value of the anterior and posterior limb of internal capsule decreased(t/Z=-2.958,-2.573,-2.085,-2.403,all P<0.05),the Kr value of the anterior limb of internal capsule decreased(t=-2.155,P<0.05),the MK value and Kr value of frontal white matter decreased(Z=-2.177,-2.711,both P<0.05).The correlation analysis showed that the MK and Kr value of the anterior limb of the internal capsule and the MK value of the posterior limb of the internal capsule were positively correlated with the score of the gross motor functional area(r=0.379,0.378,0.405,all P<0.05),and the MK value of the posterior limb of the internal capsule was positively correlated with the fine motor functional area(r=0.461,P=0.006).The Kr value of the thalamus had the largest area under the curve at 0.721 when diagnosing GDD.Conclusion Children with GDD have changes in brain microstructure,and DKI has a certain value for diagnosis.

Objective To observe the difference and clinical significance of expression levels of microRNA-155(miR-155)mRNA and interleukin-6(IL-6)in very preterm neonates with preeclampsia.Methods Twenty-eight cases of very preterm newborns(gestational age<32 weeks and/or body weight<1500 g)from preeclampsia pregnant women admitted to the department of obstetrics of Liaocheng People's Hospital from January to December 2021 were selected as the observation group,and 26 cases of very preterm neonates hospitalized for other reasons during the same period were selected as the control group.Electronic medical record clinical data related to children were collected,and the differences between the two groups were compared,including general conditions of preterm infants and pregnant mothers(gender,gestational age,birth weight,preeclampsia or not),proportion of invasive ventilation,proportion of bronchopulmonary dysplasia(BPD),incidence of acute respiratory distress syndrome(ARDS)and early-onset sepsis,white blood cell count(WBC),neutrophil count(NEUT),and expression of miR-155 mRNA and IL-6 levels in the serum of umbilical arterial blood after birth.Pearson correlation analysis was used to analyze the correlation between miR-155 and IL-6 levels Results The birth body weight of the observation group was significantly lower than that of the control group(kg:1.21±0.22 vs.1.32±0.33,P<0.05),the proportion of invasive ventilation,the proportion of BPD,the incidence of ARDS and sepsis were significantly higher than those in the control group[the proportion of invasive ventilation:75.0%(21/28)vs.57.7%(15/26),the proportion of BPD:35.7%(10/28)vs.11.5%(3/26),incidence of ARDS:100.0%(28/28)vs.84.6%(22/26),incidence of sepsis:71.4%(20/28)vs.53.8%(14/26),all P<0.05],the level of miR-155 mRNA expression and IL-6 were significantly higher than those in the control group[miR-155 mRNA(2-ΔΔCt):0.93±0.18 vs.0.17±0.03,IL-6(ng/L):73.84(33.44,429.00)vs.19.05(9.30,47.20),both P<0.05].Pearson correlation analysis showed that miR-155 and IL-6 levels were significantly positively correlated(r=0.782,P<0.01).With the extension of birth time,both WBC and NEUT gradually decreased in the two groups,and there were statistically significant differences in WBC and NEUT at each time point after birth,with counts significantly lower at 48 hours and 72 hours compared to 24 hours after birth(both P<0.05).The WBC of the observation group at 24,48 and 72 hours after birth was significantly lower than that of the control group(×109/L:7.85±2.44 vs.12.28±6.81 at 24 hours after birth,7.31±3.53 vs.10.98±7.91 at 48 hours after birth,4.97±2.05 vs.7.82±4.65 at 72 hours after birth,all P<0.05),NEUT in observation group was significantly lower than of control group at 24 hours and 48 hours after birth(×109/L:24 hours after birth was 4.13±1.93 vs.7.45±5.67,48 hours after birth was 3.96±2.64 vs.6.89±6.24,both P<0.05).Conclusion The expression level of miR-155 mRNA and IL-6 in very preterm neonates with preeclampsia is significantly up-regulated at the time of birth,and the inflammatory response of the body is disturbed,which has certain value for early assessment of the disease.

Objective:To clarify the effects of microwave radiation on anxiety-like behavior, the histomorphology of the secondary visual cortex, and calcium activity in neurons.Methods:36 C57BL/6N mice were selected and divided into control group and microwave radiation group according to the random number table method. In the simple behavioral testing, there were 8 mice in the control group and 7 mice in the radiation group. Combining fiber optic recording with behavioral experiments, there were 8 mice in the control group and 7 mice in the radiation group. Hematoxylin-eosin (HE) staining was conducted with 3 mice in each group. A high-power microwave simulated source in the X-band with a center frequency of 9.875 GHz and an average power density of 12 mW/cm 2 was used to irradiate the mice for 15 minutes, establishing a microwave radiation animal model. Then, anxiety-like behavior changes in the radiation group were identified using the open-field and elevated plus maze (EPM) tests. The effects of microwave radiation on the histomorphology of the secondary visual cortex were investigated using HE staining and optical microscopy. Based on the genetically encoded calcium imaging technique, as well as optical fiber recording combined with behavioral paradigms in the open field and the EPM, the changes of calcium activity in neurons in the V2M region of the secondary visual cortex were detected. Results:Compared to the control group, the radiation group showed a significant decrease in the frequency of exploring the central region of the open field and the open arm of the EPM ( t = 2.24, 3.10, P < 0.05). Furthermore, the radiation group exhibited the degeneration and apoptosis of some neurons in the secondary visual cortex, primarily manifested as pyknosis and deep staining, cell body shrinkage, and the slightly widening of perivascular space. Fiber optic recordings and behavioral experiments indicated that compared to the control group, mice in the radiation group exhibited significantly increased calcium activities in neurons of the secondary visual cortex when exploring the central region of the open field ( t = -2.75, P < 0.05) or the open arm of the EPM ( t = -2.77, -3.41, P < 0.05) compared to those before radiation after microwave exposure. Conclusions:Microwave radiation can induce anxiety-like behaviors and histopathological changes in the secondary visual cortex. Increased calcium activity in neurons of the secondary visual cortex is proved to be an important mechanism underlying the changes in anxiety-like behavior due to microwave radiation.

Objective:To establish a pediatric visualized teaching network containing disease images and videos, and to investigate its application effect in assisting the integrated online-offline teaching of pediatric students.Methods:The medical students of classes 2014 and 2015 in the eight-year program who studied as an intern in Department of Pediatrics, Peking Union Medical College Hospital, were enrolled as subjects. The medical students of class 2014 before the application of the pediatric visualized teaching network in the integrated online-offline teaching of pediatrics were enrolled as control group ( n=75), and the medical students of class 2015 after the application of the network were enrolled as experimental group ( n=64). The two groups were compared in terms of the results of group interview and the scores of clinical competency self-assessment scale before and after teaching assisted by the pediatric visualized teaching network. SPSS 26.0 software was used to perform a statistical analysis, with a significance level of α=0.05. Results:During the interview, most students thought that the visualized teaching network improved their learning interest in pediatrics and reduced the emotion of fear of difficulties when they just entered the pediatric internship. They were more confident in operation, and there were also increases in the degree of participation and success rate of operation. There were significant differences between the control group and the experimental group in the scores of six dimensions of the clinical competency self-assessment scale, professional competence [(3.1±0.4) vs. (4.2±0.6), P<0.001], knowledge and skills [(3.7±0.9) vs. (4.2±0.8), P<0.001], patient care [(3.7±0.8) vs. (4.3±0.6), P<0.001], communication and cooperation [(3.7±0.4) vs. (4.2±0.7), P<0.001], teaching ability [(3.8±0.5) vs. (4.3±0.8), P<0.001], lifelong learning [(3.9±0.6) vs. (4.4±0.6), P<0.001]. Conclusions:The visualized teaching network promotes the transformation of offline teaching to integrated online-offline teaching and the optimization of clinical competency-oriented teaching system.

This study intends to establish a colorectal cancer(CRC)organoid model,expand and isolate CRC-reactive tumor-infiltrating lymphocytes(TILs),screen tumor-specific T cell receptors(TCRs)and perform functional verification,in order to provide a technological platform and research foundation for the clinical transformation of individualized adoptive T-cell immunotherapy for colorectal cancer.An organoid model derived from colon cancer patient tissues was constructed using in vitro 3D culture techniques,which then subjected to HE staining and immunohistochemistry for detecting morphological characteristics and representative molecular expression.Subsequently,CRC organoids were co-cultured with TILs for sorting reactive TILs using flow cytometry,and the characteristics of reactive TCR clones was analyzed through single T cell receptor gene cloning technology.Furthermore,the function of TCRs was verified through cytotoxicity experiments.Morphological analysis and representative molecules(CK20 and CDX2)expression indicated that there is high similarity between colorectal cancer organoids and patient tumors.In the in vitro expanded and cultured TILs,colorectal cancer-reactive T cells with upregulated CD137 expression and increased IFN-γ secretion were screened out successfully,among which TCR2-T cells demonstrated superior tumor reactivity and in vitro tumor killing function.In conclusion,a platform for screening and function validation of reactive TCRs based on CRC-Org has been established,providing a technological platform for the translational application of individualized T-cell therapy for colorectal cancer.