Objective: To understand the microclimate in primary and secondary school classrooms for the study period during the winter heating season, so as to provide a reference for the revision and improvement of relevant health standards. Methods: In December 2024, stratified random sampling was used to select 30 primary and secondary schools and 180 classrooms from the northern regions with centralized heating (Liaoning Province, Tianjin City) and the southern regions without centralized heating (Shanghai City, Anhui Province, and Jiangxi Province). Indoor temperature, relative humidity, wind speed, CO 2 and other indicators were measured on site. Variance analysis, t-test, Mann-Whitney U test and Kruskal-Wallis H test were used to analyze the differences in the microclimate of classrooms among regions and urban and rural differences. Results: The average temperature in the middle of the classrooms tested on site was (16.47±4.72)℃, and the variance analysis showed that the difference between the regions was statistically significant ( F=27.80, P <0.01). Among them, Tianjin had the highest average temperature of (20.43± 2.12 )℃, followed by Liaoning (19.03±2.23)℃, Shanghai (15.33±5.32)℃, Anhui (12.79±1.74)℃, and Jiangxi (11.69± 1.68 )℃. Horizontal temperature difference was 0.90 (0.50, 1.60)℃, the vertical temperature difference was 0.20 (0.10,0.60)℃, the average relative humidity was (44.39±16.16)%, the wind speed was 0.03(0.01,0.11)m/s, and the differences among different provinces and cities were statistically significant ( H/F =40.62, 82.69, 95.06, 55.28, all P <0.01). The average CO 2 volume concentration in urban areas of Tianjin, Liaoning, and Shanghai was 0.21(0.16,0.30)%, and there was no statistically significant difference ( H=4.65, P =0.10). There were grade differences in relative humidity ( F =3.71, 6.21) and CO 2 ( H =14.72, 12.92) in the north and the south (all P <0.05). In addition, the temperature, relative humidity, wind speed and CO 2 in the middle of the classroom were 42.8%, 67.8%, 100.0% and 22.2% respectively. Conclusions The temperature in the middle of the classroom in the non centralized heating area is lower than the standard, the relative humidity of classroom in the centralized heating area is lower than the standard，and the CO 2 in the classroom in winter is lower than the standard. It is recommended to install heating facilities in schools with low temperatures to increase the temperature and increase the frequency of ventilation in classrooms or adopt mechanical ventilation strategies to reduce CO 2 volume concentration.

Aging has emerged as a cutting edge and hotspot in global life science field， with anti-aging and geriatric disease prevention and treatment becoming critical issues urgently demanding solutions in international medical communities. In the face of the challenge of accelerating global population aging， in-depth exploration of aging mechanisms and the development of effective intervention strategies hold significant scientific and clinical value. This study supported by the national key research and development program of China， employed the essence-Qi-spirit theory of Qiluo doctrine as its guiding framework， focusing on the key scientific issue of the core traditional Chinese pathogenesis of aging， namely "depletion of kidney essence， deficiency of primordial Qi， and impairment of body and spirit". The treatment principle of "tonifying the kidney to replenish essence， harmonizing Yin and Yang， warming and invigorating primordial Qi， and nourishing the body and spirit" was established. Centered on holistic aging， systemic aging， and aging-related diseases， the research integrated multidisciplinary research approaches to construct multi-modal aging models and a multi-dimensional evaluation system， and it utilized multi-omics technologies to deeply analyze aging mechanisms. By systematically reviewing historical kidney-tonifying and anti-aging formulas and combining big data with artificial intelligence technologies， an information database of anti-aging traditional Chinese medicine substance was developed to reveal the differences and synergistic effects of various treatment methods and formulas on anti-aging. Based on this treatment method， the research integrated two millennia of kidney-tonifying medicinal experience to develop the innovative anti-aging traditional Chinese medicine， namely Bazhi Bushen capsules. It was validated that this capsule can delay holistic and systemic aging through multiple targets and mechanisms， thereby elucidating the scientific connotation of the essence-Qi-spirit theory of Qiluo doctrine in guiding anti-aging research from multiple dimensions and providing robust support for leveraging the advantages of traditional Chinese medicine to occupy the commanding heights of international anti-aging research.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

OBJECTIVE: To explore the effects of electroacupuncture (EA) on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells (GCs) in patients with polycystic ovary syndrome (PCOS) and phlegm-dampness syndrome. METHODS: In this randomized controlled trial, 90 infertile women with PCOS and phlegm-dampness syndrome were recruited between August 2022 and December 2022. Patients were randomly assigned to the EA and control groups using a random sequence of codes in the order of enrolment, with 45 in in each group. Both groups underwent the ovarian stimulation protocol. The patients in the EA group received EA therapy including Zhongwan (CV 12), Qihai (CV 6), bilateral Xuehai (SP 10), Sanyinjiao (SP 6), Yinlingquan (SP 9), Tianshu (ST 25), Zusanli (ST 36), and Fenglong (ST 40), and the patients in the control group was treated with pseudo-acupuncture. The intervention was 25 min twice a week for a total of 6 times until the trigger day after menstruation had ended in the cycle before oocyte retrieval. The primary outcomes were clinical pregnancy rate (CPR) and the number of high-quality embryos. The secondary outcomes were (1) pregnancy-related indicators, including fresh embryo transfer rate (ETR), ovarian hyperstimulation syndrome (OHSS) rate, early pregnancy loss rate (ePLR), ectopic pregnancy rate, live birth rate (LBR), and cumulative CPR; (2) mitochondrial autophagy and mitochondrial membrane potential (MMP) in GCs; and (3) scoring for Chinese medicine syndrome. Adverse events to assess clinical safety were also monitored. RESULTS: The cumulative CPR was significantly higher in the EA group (42/45, 93.3%) than in the control group (38/45, 84.4%, P=0.036). The number of high-quality embryos and fresh ETR in the EA group were higher than those in the control group (3.80±1.65 vs. 2.44±1.34, P<0.001; 46.7% vs 24.4%, P=0.028). Ectopic pregnancies were not observed in either group. There were no significant differences in the fresh CPR, OHSS rate, ePLR or LBR between the two groups (P>0.05). Compared with the control group, the EA group showed lower expression levels of miR-146a-5p mRNA and P62 protein in GCs and higher levels of MMP and the LC3-II/LC3-I protein ratio (all P<0.01). The phlegm-dampness syndrome scores of the EA group were significantly lower than those of the control group (P<0.01). CONCLUSIONS EA significantly improved pregnancy outcomes in patients with PCOS and phlegm dampness syndrome. Mechanistically, this effect may be related to EA in decreasing miR-146a-5p mRNA expression, promoting mitochondrial autophagy in GCs, and improving mitochondrial function, which may contribute to improved oocyte quality. (Trial registration No. ChiCTR2200062915).
Humans ; Female ; Polycystic Ovary Syndrome/therapy* ; Pregnancy ; Electroacupuncture ; Granulosa Cells/metabolism* ; Adult ; Mitochondria/metabolism* ; Pregnancy Outcome ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Infertility, Female/therapy*

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

OBJECTIVES: This systematic review examines recent pharmacoeconomic literature on denosumab' cost-effectiveness for bone metastasis treatment, providing evidence-based insights to guide healthcare policy decisions. METHODS: A comprehensive literature search was performed across Cochrane, PubMed, EMBASE (Ovid), CNKI, and Wanfang databases to identify original articles published between 2017 and 2023. Key words consisted of bone metastases, denosumab, and cost-effectiveness in the search strategy. The methodological quality of the included studies was assessed utilizing the revised Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022). Data was extracted regarding methodological characteristics and cost-effectiveness analyses. RESULTS: A total of 111 studies were retrieved, of which 6 met the inclusion criteria. All included studies were based on clinical trials and published literature data and exhibited high methodological quality. Up to 83% (5 out of 6) of comparisons demonstrated that denosumab was more cost-effective or dominant compared to zoledronic acid. The adjusted incremental cost-effectiveness ratios varied substantially by tumor type, ranging from CZK 436,339.09 to USD 136,234 per skeletal-related event avoided and from CZK 61,580.95 to USD 118,392.11 per quality-adjusted life year gained. CONCLUSIONS The majority of the included studies support denosumab as a more cost-effective treatment option for bone metastases in solid tumors compared to zoledronic acid. The application of CHEER (2022) enhances the reliability of pharmacoeconomic evaluations.
Denosumab/therapeutic use* ; Humans ; Bone Neoplasms/economics* ; Cost-Benefit Analysis

OBJECTIVE: To investigate the biomechanical characteristics of retrograde tibial nailing (RTN) and distal tibial L-shaped plating in the internal fixation of distal tibial fractures. METHODS: Fourteen fresh adult tibia specimens were selected, comprising 7 males and 7 females aged from 34 to 55 years old. The specimens were randomly divided into experimental group and control group by numerical table method with 7 specimens in each group. RTN was used for internal fixation of distal tibial fractures in the experimental group, and L-shaped plate was used for internal fixation of distal tibial fractures in the control group. The axial compression properties of the two groups of specimens were tested under the pressure of 100, 200, 300, 400, and 500 N after operation, and torsional resistance at torque levels of 1.0, 2.0, 3.0, 4.0, 5.0 N·m. The anti-fatigue performance of the specimens was tested at 500 N pressure for 3 000 and 10 000 cycles. X-ray fluoroscopy was performed to observe whether the the internal fixator was deformed and whether the screw was loosened or broken. RESULTS: When the pressure was 400 N and 500 N, the axial compression displacement of the experimental group was (1.11±0.06) mm and (1.24±0.05) mm, which were smaller than those of the control group (1.21±0.08) mm and (1.37±0.11) mm, and the differences were statistically signific (P<0.05). Under the pressure of 500 N, the axial compression stiffness of the experimental group was (389.24±17.79) N·mm^-1, which was significantly higher than that of the control group (362.37±14.44) N·mm^-1(P<0.05). When the torque was 4 and 5 N·m, the torsion angles of the experimental group were (2.97±0.23) ° and (3.41±0.17) °, which were smaller than those of the control group (3.31±0.28) ° and (3.76±0.20) °, and the differences were statistically significant (P<0.05). When the torque was 5 N·m, the torsional stiffness of the experimental group was (1.48±0.07) N·m per degree, which was higher than that of the control group (1.36±0.06) N·m per degree, and the difference was statistically significant (P<0.05). For the intragroup comparison of fatigue resistance, the differences in axial compression displacement between the two groups were not statistically significant at 3 000 and 10 000 cycles (all P>0.05). When 3 000 times and 10 000 times of compression, the axial compression displacement of the experimental group was (1.38±0.08), (1.43±0.07) mm, which was smaller than that of the control group (1.51±0.10), (1.54±0.08) mm, the differences were statistically significant (P<0.05). In the experimental group, no screw loosening, fracture or internal fixation deformation was found, while in the control group, locking screw loosening occurred in 2 models after 10 000 pressures. CONCLUSION The biomechanical performance of RTN is obviously better than that of the distal tibial L-shaped plate, which provides biomechanical data support for the clinical application of RTN.
Humans ; Female ; Male ; Adult ; Tibial Fractures/physiopathology* ; Middle Aged ; Biomechanical Phenomena ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Bone Nails ; Tibia/surgery*

Objective:To explore the efficacy of deep learning-based automatic segmentation technology in the segmentation of hepatocellular carcinoma (HCC) lesions using gadoxetate disodium-enhanced MRI (EOB-MRI), and to investigate the prognostic value of radiomics analysis in predicting patient outcomes.Methods:This was a cross-sectional, retrospective study that collected data from 352 patients with solitary HCC who underwent imaging at the Harbin Medical University Cancer Hospital between June 2015 and May 2023. The patients were randomly divided into a training set ( n=213) and a validation set ( n=139) in a 3∶2 ratio using weighted random sampling. Two radiologists manually annotated the lesions. Hepatobiliary-phase EOB-MRI images were standardized, and six deep learning models,nnU-Net, nnFormer, UnetR, Swin-UnetR, UnetR++ and MedNeXt,were trained for automatic segmentation on the training set. The segmentation performance was evaluated on the validation set, and the segmentation efficacy was assessed using the Dice coefficient and 95% Hausdorff distance (HD 95), identifying of the optimal model. Radiomics features were extracted from both manual and automatic segmentation regions, and the radiomics score (Radscore) was calculated to stratify patients into high-risk and low-risk groups. Kaplan-Meier curves and log-rank tests were used to analyze the differences in relapse-free survival (RFS) and overall survival (OS) between the different stratified groups. Results:Among the automatic segmentation models, the MedNeXt model performed best in the validation set, with a Dice coefficient of 76.0%, HD 95 of 7.2, and a segmentation success rate of 90.6% (126/139). The nnFormer model was the second-best, with a Dice coefficient of 75.3%, HD 95 of 10.1, and a segmentation success rate of 89.9% (125/139). Other models showed Dice coefficients ranging from 66.3% to 74.1%. A MedNext-nnF model was established by combining the MedNeXt and nnFormer models, achieving a Dice coefficient of 78.2%, HD 95 of 5.9, and a segmentation success rate of 92.1% (128/139) in the validation group. After constructing the automatic segmentation radiomics prognostic model, patients were stratified by Radscore. Both manual and automatic segmentation models showed statistically significant differences in RFS and OS between different risk groups ( P<0.001). Conclusions:The Mednext-nnF fusion model enables efficient and automated segmentation of HCC lesions in EOB-MRI. The radiomics model constructed based on the automated segmentation demonstrates strong performance in predicting and stratifying prognostic risk.

Objective:To examine the near-complete genomic analysis of norovirus (NoV) subtype GⅡ.17 [P17] outbreaks in Beijing Chaoyang District from 2014 to 2024.Methods:Data and specimens related to outbreaks of the NoV aggregation in Beijing′s Chaoyang District from 2014 to 2024 were collected. The NoV was identified using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). Specimens with positive nucleic acid were amplified by standard PCR, whole genome sequencing and evolutionary analysis. Amino acid site variations were compared.Results:In Chaoyang District, from 2014 to 2024, a total of 637 aggregated outbreaks caused by the NoV infection were reported, of which 584 were successfully typed. The epidemic caused by the GⅡ.17 [P17] subtype accounted for 8.79% (56/637), which was the dominant epidemic gene subtype in 2014-2015, sporadic in 2016-2019, reappeared in 2022, and significantly increased in 2024 (27.27%, 24/88). Outbreaks caused by the GⅡ.17 [P17] subtype occurred mainly from October to December, with the main sites of occurrence in primary schools and kindergartens. This study yielded 53 near-complete genome sequences of the GⅡ.17 [P17] subtype from 46 incidents in Chaoyang District. The GⅡ.17 [P17] subtype sequences of Chaoyang District from 2014 to 2024 were segmented into three subgroups on the evolutionary tree, with sequences from 2014 to 2019, 2022 to April 2024, and May to December 2024 clustered into the d, e, and b subgroups, respectively. In the VP1 region′s P2 area, particularly at the HBGA binding site, subgroups b and e exhibited mutations in 22 and two sites, while subgroups b and e showed mutations in four and one sites, predominantly in the RdRp region.Conclusion:The outbreak caused by the NoV GⅡ.17 [P17] subtype in Chaoyang District from 2014 to 2024 continues, with a significant increase in 2024, and it becomes the dominant gene subtype from October to December. The sequence formation of the NoV GⅡ.17 [P17] subtype in Chaoyang District from January to April 2022 and from May to December 2024 shows two different evolutions, with specific mutation sites, requiring continuous monitoring of the NoV GⅡ.17 [P17] subtype.