Abuse of amphetamine-based stimulants is a primary public health concern. Recent studies have underscored a troubling escalation in the inappropriate use of prescription amphetamine-based stimulants. However, the neurophysiological mechanisms underlying the impact of acute methamphetamine exposure (AME) on sleep homeostasis remain to be explored. This study employed non-human primates and electroencephalogram (EEG) sleep staging to evaluate the influence of AME on neural oscillations. The primary focus was on alterations in spindles, delta oscillations, and slow oscillations (SOs) and their interactions as conduits through which AME influences sleep stability. AME predominantly diminishes sleep-spindle waves in the non-rapid eye movement 2 (NREM2) stage, and impacts SOs and delta waves differentially. Furthermore, the competitive relationships between SO/delta waves nesting with sleep spindles were selectively strengthened by methamphetamine. Complexity analysis also revealed that the SO-nested spindles had lost their ability to maintain sleep depth and stability. In summary, this finding could be one of the intrinsic electrophysiological mechanisms by which AME disrupted sleep homeostasis.
Animals ; Methamphetamine ; Electroencephalography ; Male ; Sleep/drug effects* ; Central Nervous System Stimulants ; Delta Rhythm/drug effects* ; Sleep Stages/drug effects*

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Objective:To investigate the protective effect of naringenin on acute lung injury related with sepsis; To discuss its possible mechanism.Methods:Totally 30 male SD rats were randomly divided into sham-operation group, model group, naringin low-, medium- and high-dosage groups, with 6 rats in each group. The sepsis-related acute lung injury model was established by cecal ligation and puncture in all groups except the sham-operation group. After modeling, naringin low-, medium- and high-dosage groups were given naringin 20 mg/kg, 40 mg/kg and 80 mg/kg, respectively for gavage, while the sham-operation group and the model group were given the same volume of distilled water by gavage, once a day, for 2 days. Pathological changes in lung tissue were observed using HE staining. The levels of 1L-1, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) were measured by ELISA; the expression of TNF-α in lung tissue was detected by immunofluorescence histopathology; the expressions of TGF-β1, TGF-βR1 and Smad2 were detected by Western Blot. An agonist group and a naringin plus agonist group were set up, with 6 mice in each group, and the expressions of TGF-β1 and Smad2 protein in the lung tissue of each group were detected by immunohistochemical staining to verify the effect of naringin on the expressions of TGF-β1 and Smad2 protein.Results:Compared with the model group, the pathological injury of lung tissue in naringin groups were obviously alleviated, and the levels of IL-1β, IL-6 and IL-18 in BALF decreased ( P<0.01), the protein expressions of TNF-α, TGF-β1, TGF-βR1 and Smad2 in lung tissue decreased ( P<0.01 or P<0.05). Further verification found that the expressions of TGF-β1 and Smad2 in the agonist group increased ( P<0.01), while the expressions of TGF-β1 and Smad2 in the naringin agonist group decreased ( P<0.01). Conclusion:Naringin can reduce the inflammatory response in the lung of the rats to protect against sepsis-related acute lung injury, and its protective effect could be related to the inhibition of the TGF-β1/Smad2 signaling pathway.

Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.

Objective To explore the effect of Lee-Silverman voice treatment (LSVT) on language re-habilitation of dysarthria in Parkinson's disease (PD).Methods A total of 84 patients with PD dysarthria ad-mitted to our hospital from February 2019 to February 2022 were selected as the research objects.According to the random number table method,they were divided into observation group and control group,with 42 cases in each group.The control group received routine speech rehabilitation training,and the observation group re-ceived LSVT for four weeks.The scores of Western Aphasia Battery (WAB) and Aphasia Quotient (AQ) be-fore and after intervention were compared between the two groups,and the differences of electroglottographic parameters such as jitter,F0,shimmer,normalized noise energy (NNE) and harmonic noise ratio (HNR) were compared between the two groups.Results Before intervention,there was no significant difference in WAB scores (listening comprehension,repetition,spontaneous speech,naming) and AQ scores between the two groups (P>0.05).After intervention,the above scores of the two groups were significantly improved,and the observation group was higher than the control group,the difference was statistically significant (P<0.05). Before intervention,the jitter,F0,shimmer,NNE,HNR of vowels "a""i""u" in the two groups were not sta-tistically significant (P>0.05).After intervention,the above-mentioned electroglottic parameters of the two groups were significantly improved.The jitter and NNE of vowels "a""i""u" in the observation group were lower than those in the control group,and the HNR was higher than that in the control group,the differences were statistically significant (P<0.05).Conclusion LSVT can improve the electroglottographic parameters and speech function of patients with PD dysarthria,and the language rehabilitation effect of PD dysarthria is obvious.

Objective To investigate the effect of hairy and enhancer of split 5(HES5)on transdifferentiation and apoptosis of renal tubular epithelial cells induced by TGF-β1 and its potential mechanism.Methods The differentially expressed genes in GSE66494 data were analyzed and screened.The mouse model of unilateral uretera obstruction(UUO)was established,and the expression level of HES5 was detected in the renal tissue.HK-2 cells were treated with 10 ng/mL TGF-β1 for 24 h to establish a tubular epithelial-mesenchymal transition(EMT)model,and then qRT-PCR and Western blotting were performed to detect the expression of HES5 at mRNA and protein levels.After HK-2 cells were transfected with the plasmid overexpressing HES5,the protein levels of fibronectin,collagen Ⅰ,vimentin,apoptosis markers Bax and Bcl2 were detected in 24 h later.Then,HK-2 cells were divided into Control group,siHES5 group,TGF-β 1 group,and siHES5+TGF-β1 group.The protein level of fibrosis and apoptosis markers were measured in above groups with Western blotting.TUNEL staining and flow cytometry were employed to detect cell apoptosis.Western blotting was applied to determine the protein levels of AKT,p-AKT,PI3K and p-PI3K.HK-2 cells overexpressing HES5 were treated with PI3K inhibitor LY294002,and the expression of vimentin was detected.Results The expression of HES5 was significantly up-regulated in both chronic kidney disease(CKD)and fibrotic kidneys of mice.Overexpression of HES5 promoted the synthesis of fibronectin,collagen Ⅰ,vimentin and Bax in HK-2 cells,and inhibited the expression of Bcl2(P＜0.05).HES5 knockdown not only down-regulated the expression of fibrosis markers,but also inhibited the apoptosis of HK-2 cells.Furthermore,HES5 knockdown inhibited the activation of PI3K/AKT signaling pathway induced by TGF-β1 in HK-2 cells(P＜0.05).Inhibitors of the PI3K/AKT signaling pathway inhibitor attenuated the induction of HES5 on vimentin.Conclusion HES5 knockdown inhibits the transdifferentiation and apoptosis in TGF-β1-induced renal tubular epithelial cells,which may be related to the decreased activity of the PI3K/AKT signaling pathway.

Facing the opportunities and challenges of pediatric education in the situation of talent emergency, this article aims to present the history of pediatric education development, offer considerations in pediatric talent cultivation from the perspective of the government, society/industry, and school in current social contexts, and provide ideas about seeking a path that can not only address the talent dilemma but also nurture pediatric talents in accordance with educational attributes. Strategies for the development of pediatric education should be guided by values and highlight child development as a priority; macro-regulate the number of enrollments based on the demand for pediatric care; and improve teaching curricula according to the development direction of the discipline. We hope to provide theoretical support for the future development of pediatric education as well as the cultivation of pediatric talents and high-quality development of child health in China.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

Objective:To explore the effect of a new teaching mode, which includes bridge-in, outcome, pre-test, participation, post-test and summary (BOPPPS), on the online teaching of radiobiology related knowledge for cancer radiotherapy practitioners.Methods:Taking the cell survival curve, cell cycle and radiosensitivity as examples, the radiotherapy practitioners in multiple university-affiliated hospitals were organized to carry out a multicenter prospective randomized control study. All practitioners were randomly divided into BOPPPS group and control group. The courses for BOPPPS group were designed as an online classroom, consisting of pre-class preparation, online teaching and post-class stages. The online teaching stage included video viewing, basic knowledge learning, literature discussion, group discussion and others. The control group employed the traditional teaching mode. The χ2 test was used to compare the consistency of general conditions between the two groups, and nonparametric test was used to compare the differences in scores between two or more groups. Results:The score of the pre-class test was 58.56 ± 0.99. Post-class average score for BOPPPS group was 85.48±0.85 and for control group 77.79±1.10, with the former being higher 7.69 ( Z=5.31, P<0.001) than the latter. The average answer time was (296.62±15.40) s for BOPPPS group and (386.41±21.27) s for control group, with the former being shorter 89.79 s ( Z=3.34, P=0.001) than latter. Subgroup analysis shown that the scores of BOPPPS group were significantly rising, regardless of whether or not the students had studied radiobiology courses. Among the students who have not studied these courses, the scores were rising greatly. Moreover, From the analysis of different positions, it was found that both the scores of BOPPPS group and control group have risen, especially for doctors, deputy chief doctors, physicists and technicians. There were also statistically differences between different degrees, with significantly rise in scores for undergraduate and doctoral students ( Z=3.64, 4.18, P<0.001). Conclusions:The flexible application of BOPPPS teaching mode to the online education of such boring disciplines, like radiobiology, is of great significance to raise the theoretical basis of radiotherapy practitioners.

Cardio-cerebrovascular disease (CCVD) is a major comorbidity of Coronavirus disease 2019 (COVID-19). However, the clinical characteristics and outcomes remain unclear. In this study, 102 cases of COVID-19 from January 22, 2020 to March 26, 2020 in Xixi Hospital of Hangzhou were included. Twenty cases had pre-existing CCVD. Results showed that compared with non-CCVD patients, those with CCVD are more likely to develop severe disease (15% versus 1%), and the proportion of pneumonia severity index grade IV was significantly higher (25% versus 3.6%). Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group (90% versus 63.4%). Compared with non-CCVD group, the levels of C-reactive protein, fibrinogen, D-dimer, and serum amyloid-A were higher, whereas the total protein and arterial partial PaO
COVID-19 ; Cerebrovascular Disorders/epidemiology* ; Comorbidity ; Humans ; SARS-CoV-2 ; Tomography, X-Ray Computed