OBJECTIVE To analyze the selection and rationales of comparators for pharmaceutical enterprises in their medical insurance access application， so as to provide a reference for promoting communication and consensus between enterprises and medical insurance authorities in this process. METHODS The application materials for drugs outside the catalogue that passed formal review published by the National Healthcare Security Administration from 2021 to 2025 were extracted， and then content analysis was used to systematically sort out relevant information of the declared drugs and comparators； the specific situations and rationales of pharmaceutical enterprises’ selection of comparators were analyzed. RESULTS A total of 1 341 declared drug documents were collected. Data analysis showed that 1 035 （77.18%） were submitted with positive comparators and 306 （22.82%） used blank comparators； 58 drugs （4.33%） took combination therapy as the reference， and 5 drugs （0.37%） referred to non-pharmacological （or non-single pharmacological） treatment regimens. Among competitive drugs declared by multiple enterprises， 50.00% of the enterprises submitted different comparators. A total of 4 basic conditions and 39 additional conditions were extracted as the rationales for selecting positive comparators. For blank comparators， 12 drug-related factors， 2 administrative factors， and 1 other factor were identified. More than 10% of the drugs did not state the rationale for comparator selection， and over 44% of drugs using blank comparators provided only one justification. CONCLUSIONS Pharmaceutical enterprises mainly select comparators based on their own interests in the medical insurance access application， and there are deficiencies in the adequacy and standardization of their selection basis and reasoning. It is recommended that enterprises follow the principled requirements of medical insurance authorities， and fully and normatively explain the reasons for selecting comparators in combination with the characteristics of their own products. Meanwhile， it is advisable to change the current open-ended statement form of selection reasons into a closed-ended answering mode， so as to highlight the priority of selection， standardize the declaration behavior of enterprises， and reduce communication divergences between the two parties.

In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (⁹⁰Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent ⁹⁰Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of ⁹⁰Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (^99mTc-MAA) perfusion test and received the ⁹⁰Y-SIRT; one patient received ⁹⁰Y-SIRT after the second ^99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of ⁹⁰Y-SIRT for treating malignant liver tumors are mild, indicating good safety.

Objective:To evaluate the effectiveness of a patient-family-centered visiting model in improving caregivers'beliefs and attitudes toward visiting patients with mental disorders.Methods:A total of 140 caregivers of inpatients diagnosed with mental disorders according to the ICD-10 were randomly assigned to an intervention group(n=71)and a control group(n=69).The intervention group participated a patient-family-centered visiting model for 4 weeks,while the control group followed routine visitation.Caregivers' beliefs and attitudes were assessed using the Beliefs and Attitudes toward Visitation in ICU Questionnaire(BAVIQ)was used to assess the improvement in caregivers' beliefs and attitudes before the intervention and at the end of the 1st,2nd,3rd,and 4th weeks after the intervention.Results:Repeated measures ANOVA showed that the belief score and attitude score of the BAVIQ questionnaire in the intervention group were significantly higher than those in the control group(Ps＜0.05)across time points.Chi-square test further confirmed that the improvement in the intervention group were significantly bet-ter than in the control group(Ps＜0.05).Conclusion:The patient-family-centered visiting model is more effective than routine visiting model in improving the caregivers' visiting beliefs and attitudes in mental health settings.

With the rapid development of artificial intelligence(AI),how to digitize the teaching of Medical Immunology is a new challenge posed by the times and education.This study is based on the advanced teaching model of Medical Immunology,which includes lectures-PAD class-flipped classrooms-expert lecture.By introducing knowledge mapping and AI teaching assistant into the entire learning process,the students not only deepen their understanding of the knowledge system of Medical Immunology,but also ex-ercise their ability to apply immunological knowledge to solve practical clinical problems,enhance their self-learning ability,expres-sion ability,communication ability,on-site performance ability,and cultivate a spirit of unity,cooperation,and exploration.The practice of empowering Medical Immunology teaching with digital intelligence achieves the integration of theory and application,the linkage between in class and out of class teaching,the connection between commonalities and individualities,and the union of abili-ties and qualities in Medical Immunology teaching.It also provides practical basis for exploring the implementation path of digital intel-ligence empowerment in Medical Immunology teaching.

Objective To investigate the spatiotemporal expression pattern of metabotropic glutamate receptor 4(mGluR4)in the mouse cochlear basilar membrane and its dynamic changes during postnatal development until hair cell synaptic maturation.Methods Ten healthy 3-month-old C57BL/6L wild-type mice(5 males,5 females,25～35 g)were bred to obtain offspring.Cochlear samples from postnatal days 1～30(P1～P30)were analyzed.Frequency-specific auditory brainstem response(ABR)thresholds were measured at 45.2,32.0,22.6,16.0,11.3,8.0,5.6,and 4.0 kHz in P12,P14,P16,P21,and P30 mice.Immunofluorescence assay combined with confocal laser scanning microscopy was used to scan cochlear whole-mount preparations.Spatiotemporal co-localization profiling of mGluR4 and synaptic markers Ctbp2 and Snap25 was observed,and quantitative comparisons of fluorescent puncta density were performed.Results ABR testing revealed undifferentiated waveforms in all P12 mice,while 70%of P14 mice exhibited well-defined Wave I.In P14,P16,P21 and P30,mice undergoing ABR testing,50%failed to exhibit ABR waveforms when stimulated by 45.2 kHz tones,and 87.5%showed no response to 32.0 kHz stimuli.Auditory response thresholds for other frequencies progressively decreased with increasing postnatal age.Immunolocalization demonstrated stronger mGluR4 expression in inner hair cells(IHCs)versus outer hair cells(OHCs).Distinct mGluR4 puncta were observed at IHC presynaptic active zones(co-localized with Snap25)as early as P11,but showed minimal overlap with CtBP2-labeled ribbons.Quantitative analysis revealed significantly higher mGluR4 puncta density at P30 compared to P14 synapses(P<0.05).Conclusion Postnatal upregulation of mGluR4 at IHC synaptic regions correlates with functional maturation.These findings suggest mGluR4 may modulate vesicular exocytosis regulation and exert pharmacological inhibition on glutamate release,potentially influencing synaptic plasticity during auditory pathway refinement.

Objective:To report the preliminary clinical exploration result of spatially fractionated radiation therapy (SFPT) using the pencil-beam-scanning (PBS) technique at a single center for the treatment of patients with bulky tumors.Methods:Data on the clinical characteristics, tumor characteristics, and dosimetric parameters were retrospectively collected from patients with bulky tumors at the Radiation Oncology Department, Ion Medical Center, First Affiliated Hospital of University of Science and Technology of China (i.e., the Hefei Ion Medical Center) from April 2024 to December 2024. Three-dimensional lattice radiotherapy (LRT) was primarily utilized in the SFRT, with multi-field robust optimization performed using pencil beam scanning. SFRT target volumes (STVs) were defined as 1.0 cm-diameter spheres. Primary observation indicators included the remission rate of tumor-associated symptoms, followed by the local tumor control rate.Results:A total of 12 patients were enrolled in this study, with a median age of 61 years (28-85 years). The primary tumors included hepatocellular carcinoma (six patients), sarcomas (three patients), and lung cancer (two patients). Eight patients received concurrent systemic therapy. The SFRT plans showed a median gross tumor volume (GTV) of 429.63 cm 3 (120.60-2 053.30 cm 3), a median STV number of 8 (3-20), a single-fraction dose to STVs of 10 GyE, a median irradiation quantity of 6 (3-8), a median STV of 8 cm 3 (3-20 cm 3), a median STV proportion of 2.09% (0.62%-3.30%), a median GTV corresponding to a single STV of 52.91 cm 3 (30.25-159.82 cm 3), and a median peak-to-valley dose ratio of 3.37 (2.29-7.60). All patients received conventionally fractionated proton therapy (CFPT), with a median prescription dose of 50 GyE (40-60 GyE). Furthermore, these patients showed a median follow-up time of 174 d (133-235 d), a remission rate of tumor-associated symptoms of 75%, and a local control rate of 100%. Four patients experienced grade 1-2 treatment-related adverse events, suggesting high overall tolerability of the patients. Conclusions:SFRT represents a promising technique with high control rates and tolerability for bulky tumors, providing the possibility for quick symptom relief and the control of tumor progression.

Quality control of pediatric musculoskeletal ultrasound(MSKUS)must be integrated throughout the entire diagnostic process.Its core lies in a thorough understanding of the growth,development,and pathophysiological characteristics of the pediatric musculoskeletal system,mastery of MSKUS examination techniques,and the establishment of a systematic and comprehensive diagnostic framework.This review focuses on the core aspects of pre-examination,during examination,and post-examination to describe the quality control points and strategies for pediatric MSKUS.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Traditionally, type 2 diabetes was regarded as a chronic, progressive metabolic disorder, with its pathogenesis considered a continuous and irreversible process. However, with advancements in diabetes research, treatment options have become more diverse, offering the potential for " diabetes remission". Achieving remission holds substantial significance for patients, their families, and society as a whole. This article provides an overview of the latest research progress on the remission of type 2 diabetes mellitus.