This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective To explore the changes of durability properties of reusable surgical gowns when used in dry and wet conditions.Methods Reusable surgical gowns made of single-layer polyester fiber or 3-layer composite material were selected as test samples,and a Martindale abrasion and pilling tester was used as the basic test platform and modified to form fixtures suitable for the wet state environment.The reusable surgical gowns underwent abrasion experiments in wet and dry conditions to observe the changes in their fiber structure,and were subjected to water penetration resistance and swelling strength tests.Results Visually the reusable surgical gowns had few changes of the microscopic textile fiber structure in dry and wet conditions,and the gowns made of single-layer polyster fiber gained advantages over the outer layers of those of 3-layer composite material in abrasion resistance with the same friction cycles.In dry and wet conditions,the hydrostatic pressure values of the gowns of single-layer polyster fiber gradually decreased with the increase of the degree of abrasion,which were always lower than those of the gowns of 3-layer composite material;the swelling strength of the gowns of single-layer polyster fiber was always greater than that of the gowns of 3-layer composite material,which decreased with the deterioration of the wear more significantly than that of the gowns of 3-layer composite material.Conclusion The reusable surgical gowns made of single-layer polyester fiber or 3-layer composite material have few differences in durability and protective properties at the early stages of ablation in dry and wet conditions.The durability of the gowns decreases as the degree of wear increases,while the trend of the decrease is slowing down until the fabric breaks down and completely loses its barrier effect.[Chinese Medical Equipment Journal,2025,46(6):28-33]

Objective:To observe the effect of Guilu Taohong Formula on semen quality in varicocele(VC)models of rats,and to explore its possible mechanism.Methods:Forty-eight male SD rats were randomly divided into four groups(sham group,model group,Guilu Taohong Formula group and L-carnitine group).After the establishment of models,the rats were treated with intra-gastric administration for eight consecutive weeks.The general condition of the rats was observed.After the gavage,the testicular and epididymal indices were calculated.Semen quality was assessed using an automatic semen analyzer.Apoptosis of testicular cells was assessed by TUNEL staining.And the expression levels of B-cell lymphocytoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and cys-teine aspartate protease-3(caspase-3)in testicular tissue were detected by Western blot.Results:Compared with the sham group,testicular index,epididymal index,sperm concentration,the percentage of progressive motility of sperm(PR％)and the expression level of Bcl-2 decreased in model group(P＜0.01).An increased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were observed in model group as well(P＜0.01).Compared with the model group,the testicular index,epidid-ymal index,sperm concentration,PR％and the expression level of Bcl-2 in Guilu Taohong Formula group increased significantly(P＜0.05,P＜0.01).A decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were de-tected in Guilu Taohong Formula group as well(P＜0.01).Similarly,the L-carnitine group showed increased testicular index,epidid-ymal index,sperm concentration,PR％and the expression level of Bcl-2 protein(P＜0.05,P＜0.01),where showed decreased ap-optosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins compared with model group(P＜0.01,P＜0.05).Conclusion:Guilu Taohong Formula improves semen quality in VC model rats and reduces the apoptosis rate of spermato-genic cells in testicular tissue,which may be related to the promotion of Bcl-2 protein expression and the inhibition of Bax and caspase-3 protein expression levels.

Objective To assess the clinical and safety outcomes of endovascular therapy(EVT)administered beyond 24 h after the onset of symptoms in patients with acute ischemic stroke(AIS)resulting from middle cerebral artery atherosclerotic occlusion.Methods We enrolled consecutive AIS patients with middle cerebral artery atherosclerotic occlusion who received EVT in our hospital between January 2020 and June 2023 and divided them into two groups based on the time from AIS onset to EVT:EVT≤24 h group and EVT＞24 h group.The National Institutes of Health Stroke Scale(NIHSS)scores after surgery,90-day functional independence(defined as mRS 0-2),symptomatic ICH(sICH),postoperative acute thrombosis,as well as mortality,were analyzed in the two groups of patients.Results A total of 161 patients were recruited,with 106 cases in the EVT≤24 h group and 55 cases in the EVT＞24 h group.The NIHSS scores declined after EVT in both groups(P＜0.01).The NIHSS scores after surgery were lower in the EVT≤24 h group(median:4.5 vs.7.0,P＜0.05).90-day functional independence(45.3％vs.30.9％,95％CI:0.93-3.68),sICH(5.7％vs.9.1％,95％CI:0.18-2.06),postoperative acute thrombosis(6.6％vs.3.6％,95％CI:0.37-9.34),and mortality(3.8％vs.1.8％,95％CI:0.23-19.42)did not differ significantly between the groups(P＞0.05).Conclusion Our findings support EVT feasibility in selected patients with middle cerebral artery atherosclerotic occlusion beyond 24 h.Prospective studies are warranted for confirmation.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:To explore the association between oral health status, the lower respiratory tract microbiome, and the frequent acute exacerbation phenotype in chronic obstructive pulmonary disease (COPD).Methods:This cross-sectional study enrolled 39 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the Department of Respiratory Medicine, Henan Provincial People′s Hospital between March 2021 and December 2022. Based on the number of hospitalization episodes for acute exacerbation in the past year, patients were divided into a frequent exacerbator group (≥2 times, n=28) and a non-frequent exacerbator group (<2 times, n=11). Bronchoalveolar lavage fluid (BALF) samples were collected from all subjects for metagenomic next-generation sequencing (mNGS). Oral health indicators and clinical data were also collected. Statistical analyses were performed using Spearman correlation analysis and multivariable Firth logistic regression analysis. Results:The frequent exacerbation group showed a significantly higher percentage of individuals with≥8 tooth loss compared to the non-frequent exacerbation group (96.4% vs 18.2%, P<0.001), a significantly younger age at first tooth loss in adulthood (53.96±7.30 years vs 62.10±5.80 years, P=0.003), and a significantly higher proportion of individuals who hardly brushed their teeth (50.00% vs 9.09%, P=0.038). The alpha-diversity indices of the lower respiratory tract microbiota were significantly lower in the frequent exacerbation group than in the non-frequent exacerbation group (all P<0.01). The relative abundances of Bacillota, Bacteroidota, Fusobacteriota, Streptococcus, Prevotella, Veillonella, Neisseria, Rothia, Prevotellamelaninogenica, Prevotellajejuni, Rothia mucilaginosa, Veillonella parvula, and Neisseria subflava were lower in the frequent exacerbation group (all P<0.05). In patients with AECOPD, the exacerbation frequency and the presence of ≥8 tooth loss were both negatively correlated with the Shannon index ( r=-0.854, P<0.001; r=-0.642, P<0.001, respectively). Further analysis revealed that Bacillota ( r=-0.862, P<0.001) and Streptococcus ( r=-0.814, P<0.001) were significantly negatively correlated with exacerbation frequency, while Pseudomonas was positively correlated with exacerbation frequency (all P<0.05). Bacillota ( r=0.369, P=0.021), Fusobacteriota ( r=0.368, P=0.021), and Veillonella ( r=0.379, P=0.017) were positively correlated with FEV 1% predicted. Multivariable Firth logistic regression analysis revealed that the first principal component of the microbial community ( OR=2.29, 95% CI: 1.20-11.07) and the loss of≥8 teeth ( OR=14.37, 95% CI: 1.42-482.51) were independent factors associated with frequent acute exacerbations. Conclusion:Frequent acute exacerbations of COPD are significant association with deteriorated oral health and dysbiosis of the lower respiratory tract microbiome, characterized by reduced alpha-diversity and depletion of commensal bacteria.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry* ; Animals ; Photochemotherapy ; Humans ; Mice ; Antineoplastic Agents/administration & dosage* ; Photosensitizing Agents/chemistry* ; Neoplasms/metabolism* ; Female ; Copper/chemistry* ; Reactive Oxygen Species/metabolism* ; Tumor Microenvironment/drug effects* ; Cell Line, Tumor ; Male

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans