ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide （LPS）-induced acute lung injury （ALI）， and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid （AA） in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight： normal group， model group， dexamethasone group （2 mg·kg^-1）， low-dose Yantiao prescription group （18 g·kg^-1）， and high-dose Yantiao prescription group （36 g·kg^-1）， with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days， and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to assess lung tissue pathology. The wet/dry weight ratio （W/D） and myeloperoxidase （MPO） activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry （LC-MS/MS）. ResultsCompared with the conditions in the normal group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the model group was significantly increased （P<0.01）. The alveolar structure in mice was severely damaged， with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased （P<0.01）. The content of AA metabolites， including prostaglandin D₂ （PGD₂）， prostaglandin E₂ （PGE₂）， 11（S）-hydroxy-eicosatetraenoic acid ［11（S）-HETE］， and 5-hydroxy-eicosatetraenoic acid （5-HETE） in serum and lung tissue was significantly increased （P<0.05）， while the content of 11，12-epoxyeicosatrienoic acid （11，12-EET） and 14，15-epoxyeicosatrienoic acid （14，15-EET） in serum was significantly decreased （P<0.01）. Compared with the results in the model group， the content of serum pro-inflammatory cytokines TNF-α， IL-1β， and IL-6 in the dexamethasone group， low-dose Yantiao prescription group， and high-dose Yantiao prescription group was significantly reduced （P<0.05）. Mild thickening of alveolar walls， scattered inflammatory cell infiltration， and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced （P<0.01）. The content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum from the dexamethasone group was significantly decreased （P<0.05）， while the content of 14，15-EET in serum significantly increased （P<0.01）， and the content of 5-HETE in lung tissue significantly decreased （P<0.01）. In the low-dose and high-dose Yantiao prescription groups， the content of AA metabolites PGD₂， PGE₂， 11（S）-HETE， and 5-HETE in serum and lung tissue was significantly decreased （P<0.05）， while the content of 11，12-EET in both serum and lung tissue was significantly increased （P<0.05）. ConclusionYantiao prescription has significant protective effects against LPS-induced ALI， which are related to its regulation of AA metabolic pathways in vivo.

Hormesis effect has been observed in the secondary metabolite synthesis of microorganisms induced by rare earth elements. However, the underlying molecular mechanism remains unclear. To analyze the molecular mechanism of the regulatory effect of Rhodotorula mucilaginosa in the presence of lanthanum chloride, different concentrations of lanthanum chloride were added to the fermentation medium of Rhodotorula mucilaginosa, and the carotenoid content was subsequently measured. It was found that the concentrations of La³⁺ exerting the promotional and inhibitory effects were 0-100 mg/L and 100-400 mg/L, respectively. Furthermore, the expression of 33 genes and the synthesis of 55 metabolites were observed to be up-regulated, while the expression of 85 genes and the synthesis of 123 metabolites were found to be down-regulated at the concentration range of the promotional effect. Notably, the expression of carotenoid synthesis-related genes except AL1 was up-regulated. Additionally, the content of β-carotene, lycopene, and astaxanthin demonstrated increases of 10.74%, 5.02%, and 3.22%, respectively. The expression of 5 genes and the synthesis of 91 metabolites were up-regulated, while the expression of 35 genes and the synthesis of 138 metabolites were down-regulated at the concentration range of the inhibitory effect. Meanwhile, the content of β-carotene, lycopene, and astaxanthin decreased by 21.73%, 34.81%, and 35.51%, respectively. In summary, appropriate concentrations of rare earth ions can regulate the synthesis of secondary metabolites by modulating the activities of various enzymes involved in metabolic pathways, thereby exerting the hormesis effect. The findings of this study not only contribute to our comprehension for the mechanism of rare earth elements in organisms but also offer a promising avenue for the utilization of rare earth elements in diverse fields, including agriculture, pharmaceuticals, and healthcare.
Lanthanum/pharmacology* ; Rhodotorula/genetics* ; Carotenoids/metabolism* ; Hormesis/drug effects* ; Fermentation ; Multiomics

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective To investigate the effect of quercetin(QUE)on the Th1/Th2 immune balance in allergic rhinitis(AR)mice via regulating protein tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Method We selected SPF-grade male BALB/c mice and constructed the AR mouse model through sensitization treatment.Seventy-two mice were randomly divided into the model group,the QUE-L group(50 mg/kg QUE by gavage),the QUE-M group(100 mg/kg QUE by gavage),the QUE-H group(200 mg/kg QUE by gavage),and the QUE-H+JAK2/STAT3 pathway activator Coumermycin A1 Group(200 mg/kg QUE by gavage+tail vein injection of 1 mg/kg Coumermycin A1),and normal mice were taken and only treated with 0.9 sodium chloride injection by intraperitoneal injection and nasal drip as the control group.The histopathological morphology of nasal mucosa in each group of mice was detected by HE staining.The levels of interferon-γ(IFN-γ),interleukin-4(IL-4),immunoglobulin E(IgE),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in the serum of mice in each group were detected by ELISA.The apoptosis rate of nasal mucosa tissue cells in each group was determined by the TUNEL method,and the protein expressions of JAK2 and STAT3 in the nasal mucosa tissues of mice in each group were detected by Western blot method.Results Compared with the control group,the model group had disorganized nasal mucosal epithelial cells,vasodilation,accompanied by severe inflammatory cell infiltration,presence of obvious pathological changes and decreased serum IFN-γ level(P<0.05).The levels of serum IL-4,IgE,IL-1β,IL-6,IL-8,the apoptosis rate of nasal mucosa tissue cells,and the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 increased(P<0.05).The nasal mucosal epithelial cells of mice in the QUE-L group,QUE-M group and QUE-H group were arranged neatly compared with those in the model group.Vasodilation and inflammatory cell infiltration were significantly alleviated,the pathological changes were significantly reduced,and the serum IFN-γ level was increased(P<0.05).The levels of serum IL4,IgE,IL-1β,IL-6,and IL-8,the apoptosis rate of nasal mucosal tissue cells,and the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 decreased(P<0.05).Compared with the QUE-H group,the QUE-H+Coumermycin A1 group had aggravated pathological changes,deteriorated inflammation levels and immune imbalance,and increased apoptosis rate of nasal mucosal tissue cells and protein expression in the JAK2/STAT3 pathway(P<0.05).Conclusion QUE may reverse the Th1/Th2 immune imbalance in AR mice by inhibiting the JAK2/STAT3 signaling pathway.

Intestinal tuberculosis (ITB) is a specific infection caused by Mycobacterium tuberculosis invading the intestinal wall, encompassing two types: primary and secondary. In clinical practice, it is more commonly secondary to extrapulmonary tuberculosis, such as cavitary pulmonary tuberculosis. In recent years, the incidence of ITB has shown an increasing trend. Due to its insidious onset and the lack of obvious or specific early symptoms, early diagnosis is challenging, often leading to a prolonged disease course. Therefore, accurate early diagnosis is of great significance for the control and prevention of ITB. Currently, the primary diagnostic methods for tuberculosis include etiological examination, histopathological evaluation, molecular biological diagnosis, and imaging studies. This article summarizes recent advances in the application of these diagnostic techniques for ITB, aiming to provide valuable insights for healthcare professionals.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective To investigate the effect of quercetin(QUE)on the Th1/Th2 immune balance in allergic rhinitis(AR)mice via regulating protein tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Method We selected SPF-grade male BALB/c mice and constructed the AR mouse model through sensitization treatment.Seventy-two mice were randomly divided into the model group,the QUE-L group(50 mg/kg QUE by gavage),the QUE-M group(100 mg/kg QUE by gavage),the QUE-H group(200 mg/kg QUE by gavage),and the QUE-H+JAK2/STAT3 pathway activator Coumermycin A1 Group(200 mg/kg QUE by gavage+tail vein injection of 1 mg/kg Coumermycin A1),and normal mice were taken and only treated with 0.9 sodium chloride injection by intraperitoneal injection and nasal drip as the control group.The histopathological morphology of nasal mucosa in each group of mice was detected by HE staining.The levels of interferon-γ(IFN-γ),interleukin-4(IL-4),immunoglobulin E(IgE),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-8(IL-8)in the serum of mice in each group were detected by ELISA.The apoptosis rate of nasal mucosa tissue cells in each group was determined by the TUNEL method,and the protein expressions of JAK2 and STAT3 in the nasal mucosa tissues of mice in each group were detected by Western blot method.Results Compared with the control group,the model group had disorganized nasal mucosal epithelial cells,vasodilation,accompanied by severe inflammatory cell infiltration,presence of obvious pathological changes and decreased serum IFN-γ level(P<0.05).The levels of serum IL-4,IgE,IL-1β,IL-6,IL-8,the apoptosis rate of nasal mucosa tissue cells,and the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 increased(P<0.05).The nasal mucosal epithelial cells of mice in the QUE-L group,QUE-M group and QUE-H group were arranged neatly compared with those in the model group.Vasodilation and inflammatory cell infiltration were significantly alleviated,the pathological changes were significantly reduced,and the serum IFN-γ level was increased(P<0.05).The levels of serum IL4,IgE,IL-1β,IL-6,and IL-8,the apoptosis rate of nasal mucosal tissue cells,and the protein expressions of p-JAK2/JAK2 and p-STAT3/STAT3 decreased(P<0.05).Compared with the QUE-H group,the QUE-H+Coumermycin A1 group had aggravated pathological changes,deteriorated inflammation levels and immune imbalance,and increased apoptosis rate of nasal mucosal tissue cells and protein expression in the JAK2/STAT3 pathway(P<0.05).Conclusion QUE may reverse the Th1/Th2 immune imbalance in AR mice by inhibiting the JAK2/STAT3 signaling pathway.

OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy (DN).METHODS From the perspective of healthcare service providers,a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN.Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months,a simulation period of 15 years and an annual discount rate of 5％.At the same time,one-way sensitivity analysis and probability sensitivity analysis were performed,and the stability of the results was validated.RESULTS Accumulative cost of the standard treatment regimen was 579329.54 yuan,and the accumulative utility was 8.0524 quality-adjusted life year (QALYs);the accumulative cost of finerenone combined with the standard treatment regimen was 332520.61 yuan,and the accumulative utility was 8.1874 QALYs.Finerenone combined with the standard treatment regimen was more cost-effective.The results of one-way sensitivity analysis showed that dialysis status utility value,DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio,but did not affect the robustness of the model.The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100％ probability.CONCLUSIONS For DN patients,finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.