Children， as a special group， frequently experience of off-label drug use worldwide. Common reasons for off-label drug use in children include the lack of data on pediatric patients during the clinical trial stage of drug development， delayed updates to drug instructions， and the non-standard professional behavior of some doctors. Off-label drug use in children is a double-edged sword. It could save lives and provide a way to explore additional functions of drugs， while it may also lead to the phenomenon of hyper-indication abuse， increasing the risk of adverse drug events. Regulating off-label drug use in children can safeguard the best treatment rights and interests of children. It is recommended to encourage pharmaceutical enterprises to conduct research and development of pediatric new drugs， simplify the approval process for drug instructions amendments， accumulate evidence-based medical evidence for off-label drug use in children， standardize the process of off-label drug use in children in medical institutions， continuously improve the standardized diagnosis and treatment capabilities of pediatricians， and actively cooperate with the families of pediatric patients in diagnosis and treatment， so as to comprehensively safeguard the rights and interests of both doctors and patients.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

OBJECTIVE: To observe the clinical efficacy of auricular electroacupuncture for post-stroke dysphagia in the pharyngeal phase. METHODS: Eighty-two patients with post-stroke dysphagia in the pharyngeal phase were randomized into an auricular electroacupuncture group (41 cases) and a swallowing electrical stimulation group (41 cases, 1 case dropped out). In the auricular electroacupuncture group, electroacupuncture was applied at auricular points, i.e. Xin (CO₁₅) and Yanhou (TG₃), using disperse-dense wave, in frequency of 2 Hz/10 Hz, 30 min a time. In the swallowing electrical stimulation group, swallowing electrical stimulation was delivered for 30 min a time. Both groups were treated once daily for 4 weeks. The functional oral intake scale (FOIS) grade, as well as the hyolaryngeal complex displacement, the pharyngeal constriction rate (PCR) and the pharyngeal delay time (PDT) under video fluoroscopic study of swallowing (VFSS) were observed before and after treatment, and the clinical efficacy was evaluated in the two groups. RESULTS: Compared before treatment, the FOIS grade was improved (P<0.01), the forward and upward displacement amplitude of hyoid bone and thyroid cartilage was increased (P<0.05), and the PCR and PDT were decreased (P<0.05) after treatment in the two groups. After treatment, compared with the swallowing electrical stimulation group, the FOIS grade was superior (P<0.01), the upward displacement amplitude of hyoid bone and thyroid cartilage was larger (P<0.05) and the PCR and PDT were lower (P<0.05) in the auricular electroacupuncture group. The total effective rate was 85.4% (35/41) in the auricular electroacupuncture group, which was higher than 62.5% (25/40) in the swallowing electrical stimulation group (P<0.05). CONCLUSION Auricular electroacupuncture can effectively trigger pharyngeal initiation and improve post-stroke dysphagia in the pharyngeal phase.
Humans ; Electroacupuncture ; Male ; Deglutition Disorders/etiology* ; Female ; Middle Aged ; Aged ; Stroke/physiopathology* ; Pharynx/physiopathology* ; Acupuncture, Ear ; Acupuncture Points ; Deglutition ; Treatment Outcome ; Adult

Chimeric antigen receptor T (CAR-T) lymphocytes are at the forefront of adoptive immunotherapy research, and this technology has significantly advanced the prospects of tumor immunotherapy. CAR-T therapy has demonstrated remarkable efficacy in haematological tumours of lymphoid origin and provided therapeutic possibility for solid tumours. Currently, CAR-T cell preparation predominantly involves transfection of T cells with viral vectors. However, the production of viral vectors is time-consuming, expensive, and the vectors have low loading capacity, along with insertion instability. Consequently, there is a pressing need to develop more convenient and precise non-viral gene delivery methods. This paper reviews the most promising non-viral gene delivery technologies, including CRISPR/Cas9 gene editing, transposon systems such as Sleeping Beauty (SB) and PiggyBac (PB), and mRNA, and anticipates the future development of non-viral vector-based CAR-T therapies.
Humans ; Immunotherapy, Adoptive/methods* ; Receptors, Chimeric Antigen/immunology* ; Animals ; Gene Transfer Techniques ; Genetic Vectors/genetics* ; Gene Editing ; CRISPR-Cas Systems/genetics* ; DNA Transposable Elements/genetics* ; T-Lymphocytes/immunology* ; Neoplasms/immunology*

At present, the C-arm structure accelerators commonly used in radiotherapy equipment are complex in operation and have potential safety hazards when realizing non-coplanar treatment. By combining with medical robotic arm technology, a spherical radiotherapy accelerator motion system is designed. The beam module is clamped by the medical robotic arm structure to achieve three-dimensional multi-angle irradiation treatment within the non-coplanar angle range. Firstly, the rotating mechanism, beam module, and MLC module of the spherical radiotherapy equipment are designed. Then, the double-plane counterweight method is used to calculate the dynamic balance of the equipment, ensuring that the beam center point does not rotate during the treatment process. Finally, the strength check and reliability analysis of the transmission component gear are conducted. The results show that the designed spherical radiotherapy accelerator motion system can meet the requirements of stable, accurate, and fast precision radiotherapy, which is conducive to improving the treatment efficiency.
Particle Accelerators/instrumentation* ; Equipment Design ; Reproducibility of Results ; Radiotherapy/instrumentation*

Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y₁₂ receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y₁₂ receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y₁₂ receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y₁₂ occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y₁₂ occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y₁₂ signaling pathway in cases of abnormal on-treatment platelet reactivity.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Objective To understand the epidemiological characteristics of scrub typhus disease and to provide a scientific basis for the prevention and control of scrub typhus disease. Methods Descriptive epidemiological methods were used to analyze the population and regional distribution of scrub typhus. Seasonal characteristics were analyzed using concentration method and circular distribution method, and incidence trend was analyzed using joinpoint regression model. Results The annual incidence rate of scrub typhus was 0.95/100 000 from 2010 to 2022. The incidence rate of male was 0.77/100 000, lower than that of female 1.12/100 000 (χ²=18.89, P<0.05). The incidence rate of the 60-74 years old group was 3.38/100,000, and the total number of cases in the age group 45-74 years was 416 (74.95%). Occupational distribution was mainly among farmers, with 448 cases (80.72%). The top three regions with the highest number of reported cases (in order: Donghai County, Ganyu District, and Guannan County) reported a total of 416 cases, accounting for 74.95%. Concentration ratio was M=0.9408, and the incidence of scrub typhus disease was strictly seasonal. Circular distribution results showed a^-=-62.3728, S=20.8960. The circular distribution results indicated that the peak day was October 19th, and the peak period was between October 7 to December 19. The average annual percentage change (AAPC) of the incidence rate from 2010 to 2022 was 13.70%, 95% CI (-8.62%~41.48%), and the incidence rate showed an upward trend (t=1.15, P=0.249). Conclusion The incidence of scrub typhus disease is strictly seasonal, and the incidence rate over the years shows an upward trend. It is necessary to strengthen monitoring and take various intervention measures to reduce the risk of scrub typhus disease.

Objective To investigate the significance of intratumoral and peritumoral radiomics models in predicting occult lymph node metastasis in stage T1 non-small cell lung cancer(NSCLC)and to compare the predictive accuracy in different peritumoral radiomics models.Methods The CT images and clinical data of 211 patients without lymph node metastasis on preoperative CT examination and pathologically confirmed NSCLC after surgery were collected.The radiomics features were derived from the three-dimensional volume of interest(VOI)of the intratumoral and peritumoral at 3-,5-,and 10-mm following lesion segmentation on CT images of each patient.The feature data of all nidus were radomly divide into training set and validation set with a ratio of 7︰3.The Pearson or Spearman correlation test was performed to remove redundancy.Dimensionality was reduced by the least absolute shrinkage and selection operator(LASSO)regression analysis.The linear combination of selected features and corresponding coefficients were used to construct the Radiomics score(Radscore).The clinical model and comprehensive model were constructed by logistic regression analysis.The conprehensive model was visualized with the nomogram,and its performance was evaluated.Results Among the peritumoral radiomics models,the peritumoral 5-mm model showed the best predictive efficacy[validation set,area under the curve(AUC)0.771].The comprehensive model containing Radscore,CT image features and CEA exhibited the best performance(validation set,AUC 0.850).Conclusion Intratumoral and peritumoral radiomics models perform efficiently in predicting occult lymph node metastasis in stage T1 NSCLC,and nomogram can effectively and noninvasively predict occult lymph node metastasis in NSCLC.