Objective To analyze the problems in the operation and management of drug clinical trials and put forward targeted suggestion. Methods An electronic questionnaire survey was conducted among medical staff in about 80 hospitals in the yangtze river delta region. Results 606 valid questionnaires were received. 71% of the respondents expressed their willingness to study and participate in drug clinical trials. There were significant differences in the cognitive demands, willingness and motivation of the respondents with different occupations and educational backgrounds about the drug clinical trial work （P<0.05）. During the operation of drug clinical trials, respondents reported the main factors affecting the quality of clinical trials which including good clinical practice (GCP) awareness and subjective enthusiasm of investigators （response rate 27%）, job stability of supervisors and research coordinators （27%）, compliance of subjects （45%）, quality control of the whole process of the circulation of test drugs, medical devices and biological samples （52%）, and the informatization level of clinical trial institutions （30%）. Conclusion Hospitals, institutions and project teams could take measures to cultivate and stabilize the drug clinical trial talent team, improve the quality management system of drug clinical trials, improve work efficiency, and promote the high-quality development of drug clinical trials in medical institutions.

The precise diagnosis and treatment of hepatocellular carcinoma （HCC） face major challenges such as the complexity of tumor microenvironment， treatment resistance， and a high risk of recurrence and metastasis. In recent years， ultrasound technology has moved beyond its traditional role in screening and localization， gradually evolving into a multidimensional therapeutic platform capable of energy activation， targeted delivery， local ablation， immune modulation， and therapeutic feedback. This article systematically reviews the latest advances in the basic research on ultrasound techniques in HCC treatment and integrated management. In terms of treatment， intervention strategies represented by microbubble/nanobubble-mediated delivery， sonodynamic therapy， high-intensity focused ultrasound， and histotripsy not only enable in situ physical destruction of lesions， but also effectively reverse tumor immune tolerance networks through deep synergy with sonogenetics， metabolic reprogramming， and immunochemotherapy. In terms of integrated management， novel sonosensitive nanodelivery systems provide a platform for energy activation and targeted controlled release. To address the translational bottlenecks in this field， it is recommended to develop standardized consensus on preclinical therapeutic ultrasound parameters， in order to establish a new translational paradigm for individualized precise diagnosis and treatment of HCC.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

Objective To explore the value of serum soluble triggering receptor expressed on myeloid cell-1(sTREM-1),interleukin-17(IL-17),and soluble Fas ligand(sFasL)in evaluating severity and prognosis of neonatal infection.Methods From November 2022 to November 2024,a total of 105 neonates with infections who visited the Department of Pediatrics in the hospital were labeled as infection group,and 105 healthy neo-nates were labeled as control group.Based on the severity of neonatal infection,the affected children were as-signed into extremely critical group,critical group,and non critical group.Based on prognosis,the affected children were grouped into adverse group and good group.Enzyme linked immunosorbent assay(ELISA)was used to measured serum sTREM-1,IL-17,and sFasL.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum sTREM-1,IL-17,and sFasL for prognosis.Results The serum levels of sTREM-1,IL-17,and sFasL in the infection group were significantly higher than those in the control group(P＜0.05).The serum sTREM-1,IL-17,and sFasL decreased in serum of extremely critical group,critical group,and non critical group in sequence(P＜0.05).Spearman correlation showed that serum sTREM-1,IL-17,and sFasL levels were positively correlated with disease severity(r=0.601,0.592,0.523,P＜0.05).The proportion of cesarean section,serum levels of sTREM-1,IL-17,and sFasL in the poor group were higher than those in the good group(P＜0.05),and the Apgar score was lower than that in the good group(P＜0.05).Logistic regression revealed that cesarean section,sTREM-1,IL-17,and sFasL were all factors affecting the adverse prognosis of neonatal infections(P＜0.05).ROC curve showed that the area under the curve(AUC)of serum sTREM-1,IL-17,sFasL,and their combined detection in predicting adverse prognosis of neonatal in-fections was 0.781,0.788,0.768,and 0.879,respectively.The AUC of joint prediction was greater than those of individual prediction(Zcombination-sTREM-1=2.238,P=0.025,Zcombination-IL-17=2.014,P=0.044,Zcombination-sFasL=2.248,P=0.025).Conclusion Serum sTREM-1,IL-17,and sFasL levels in neonates with infections are man-ifestly elevated,and they are closely related to the severity and prognosis.

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

Objective:To explore the effects of IFN-γ on IL-8 secretion by human liver cancer cells and the impact on their malignant biological functions in vitro. Methods:HuH7 and Hep3B cells were treated with different concentrations of IFN-γ for 24 or 48 h. Changes in the cellular activity, IL-8 secretion, and the proportion of CD133 + liver cancer stem cells were evaluated using CCK8 kit and flow cytometry. Western blot was used to detect the effects of IFN-γ on the expression of several molecules such as phosphorylated protein kinase B (p-Akt), phosphorylated c-Jun N-terminal kinase (p-JNK), vimentin, and E-cadherin in the liver cancer cells. Effects of IFN-γ with or without IL-8 on the migration of liver cancer cells were detected by transwell assay. Additionally, effects of IFN-γ combined with IL-8 or IL-8 receptor inhibitor repertaxin on the differentiation of liver cancer stem cells were detected by flow cytometry. One-way analysis of variance and Tukey-Kramer test were used for statistical analysis. Results:HuH7 and Hep3B cells secreted significantly higher levels of IL-8 than normal hepatocytes LO2 ( P<0.01) and high expression level of IL-8 gene ( CXCL8) was closely correlated with the expression levels of vimentin gene ( VIMENTIN), CD133 gene ( PRCM1), PD-L1 gene ( CD274), PD-1 gene ( PDCD1), and CD163 gene ( CD163), as well as the poor prognosis of liver cancer patients ( P<0.01). IFN-γ (1-100 ng/ml) had no significant effect on the proliferative activity of HuH7 and Hep3B cells ( P>0.05), but could significantly inhibit IL-8 secretion, cell migration, CD133 + liver cancer stem cell differentiation and suspension tumor sphere formation through the Akt and JNK pathways ( P<0.01). IFN-γ combined with IL-8 could significantly reversed the inhibitory effects of IFN-γ on liver cancer cell migration, stem cell differentiation, and suspension tumor sphere formation ( P<0.01). IFN-γ in combination with repertaxin could synergistically inhibited the differentiation of CD133 + liver cancer stem cells ( P<0.01). Conclusion:IFN-γ inhibits the differentiation and migration of human liver cancer cells through the Akt/JNK-IL-8 signaling pathway, providing a new strategy for future clinical immunotherapy of liver cancer.

Objective:To explore the differences in quality of life among patients with olfaction disorders (OD) due to various etiologies and to identify factors influencing olfactory-related quality of life.Methods:This cross-sectional study enrolled patients with OD who visited the Department of Otolaryngology at Fudan University Eye, Ear, Nose, and Throat Hospital between February and June 2024. Psychophysical olfactory test was performed using the Chinese Smell Identification Test (CSIT), which was based on the Chinese population, with the TDI score used as the total score for threshold (T), discrimination (D), and identification (I) tests. The quality of life related to OD was assessed using a brief version of the Questionnaire of Olfactory Disorders (bQOD), which included QOD-P, QOD-Q, and QOD-VAS. Visual analog scales (VAS) was used to rate the degree of subjective decline in olfaction. Statistical analysis was conducted to assess the impact of etiologies, age, gender, onset time, psychophysical olfactory tests, and subjective assessment on olfactory-related quality of life.Results:A total of 419 patients were enrolled, including 220 males and 199 females, with the age of (39.72±14.31) years (range: 5 to 76 years). Among the 419 patients, 380 completed the bQOD and VAS assessment. The results showed that there were intergroup differences in the QOD-P and QOD-Q scores among patients with OD caused by different etiologies ( P values were 0.001 and 0.003, respectively). The QOD-P score was negatively correlated with age ( P<0.05), and positively correlated with the TDI score ( P<0.01). The QOD-Q score was negatively correlated with disease duration ( P<0.05), and positively correlated with the patients′ subjective olfactory decline as assessed by the VAS score ( P<0.01), and had no significant correlation with psychophysical olfactory tests. Female patients had lower QOD-Q scores than male patients ( P<0.05). The QOD-VAS score was positively correlated with the patients′ subjective olfactory impairment ( P<0.01) and showed no significant correlation with psychophysical olfactory tests. Female patients had worse QOD-VAS scores than male patients ( P<0.05). Conclusion:Compared with psychophysical olfactory tests, VAS olfactory scores are more closely related to quality of life. Different etiologies, duration of the disease, and gender also affect olfactory-related quality of life.

Objective:To explore the differences in quality of life among patients with olfaction disorders (OD) due to various etiologies and to identify factors influencing olfactory-related quality of life.Methods:This cross-sectional study enrolled patients with OD who visited the Department of Otolaryngology at Fudan University Eye, Ear, Nose, and Throat Hospital between February and June 2024. Psychophysical olfactory test was performed using the Chinese Smell Identification Test (CSIT), which was based on the Chinese population, with the TDI score used as the total score for threshold (T), discrimination (D), and identification (I) tests. The quality of life related to OD was assessed using a brief version of the Questionnaire of Olfactory Disorders (bQOD), which included QOD-P, QOD-Q, and QOD-VAS. Visual analog scales (VAS) was used to rate the degree of subjective decline in olfaction. Statistical analysis was conducted to assess the impact of etiologies, age, gender, onset time, psychophysical olfactory tests, and subjective assessment on olfactory-related quality of life.Results:A total of 419 patients were enrolled, including 220 males and 199 females, with the age of (39.72±14.31) years (range: 5 to 76 years). Among the 419 patients, 380 completed the bQOD and VAS assessment. The results showed that there were intergroup differences in the QOD-P and QOD-Q scores among patients with OD caused by different etiologies ( P values were 0.001 and 0.003, respectively). The QOD-P score was negatively correlated with age ( P<0.05), and positively correlated with the TDI score ( P<0.01). The QOD-Q score was negatively correlated with disease duration ( P<0.05), and positively correlated with the patients′ subjective olfactory decline as assessed by the VAS score ( P<0.01), and had no significant correlation with psychophysical olfactory tests. Female patients had lower QOD-Q scores than male patients ( P<0.05). The QOD-VAS score was positively correlated with the patients′ subjective olfactory impairment ( P<0.01) and showed no significant correlation with psychophysical olfactory tests. Female patients had worse QOD-VAS scores than male patients ( P<0.05). Conclusion:Compared with psychophysical olfactory tests, VAS olfactory scores are more closely related to quality of life. Different etiologies, duration of the disease, and gender also affect olfactory-related quality of life.

Objective To explore the association between the growth condition of mandibular third molars(M3)and the parameters of mandibular dental arch through a retrospective cross-sectional study on M3 in adults,and to provide a basis for the selection of clini-cal treatment of M3.Methods A total of 221 adult patients were randomly selected for our study.Dolphin software was used to analyze the CBCT of all the patients.Parameters of the mandibular dentition including the entire dental crowding(EDC)were recorded.Then the association between M3 growth condition and these parameters was analyzed.Results The mesio-impacted angle of M3 was posi-tively correlated with EDC(P＜0.05),and negatively correlated with the retromolar space(RMS,P＜0.0 1).It was worth noting that me-dian mesio-impacted M3 significantly increased EDC(P＜0.01),and the erupting M3 in the vertical orthotopic position significantly in-creased RMS(P＜0.01).Conclusion For patients with median mesio-impacted M3 or insufficient RMS,preventive removal of M3 may be considered clinically,which may help to reduce crowding and prevent relapse after orthodontic treatment.