Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

Objective:To establish an environmental management strategy for the prevention of ventilator-associated pneumonia from the perspective of etiological characteristics and to verify its application effect.Methods:Based on a sampling survey, this study constructed preventive management strategies for ventilator-associated pneumonia by blocking pathogen characteristics from the perspective of both colonization and infection management in patients. From July 2021 to June 2023, a non-synchronous randomized controlled study was conducted, including a control group of 59 cases and an experimental group of 57 cases from ICU of Tianjin Teda Hospital, all of them were mechanically ventilated patients. The effectiveness of the strategy was confirmed.Results:In the control group, there were 35 males and 24 females, with an average age of (46.97 ± 18.84) years. In the experimental group, there were 39 males and 18 females, with an average age of (47.49 ± 13.85) years. During the study period, there were 9 cases of ventilator-associated pneumonia (VAP) in the control group and 2 cases in the experimental group, the difference between the two groups was statistically significant (exact odds ratio=0.031). The duration of mechanical ventilation in the experimental group (122.41 ± 18.36) h, which was shorter than that in the control group (187.62 ± 18.05) h, and the difference was statistically significant ( t=19.28, P<0.05). The length of ICU stay in the experimental group was (8.38 ± 0.79) d, in the control group was (10.99 ± 1.10) d, the difference between them was statistically significant ( t=14.66, P<0.05). On the 7th day, there were 7 cases of positive pathogenic bacteria in sputum culture in the experimental group, which was significantly different from the 29 cases in the control group ( χ2=16.73, P<0.05). Conclusions:The vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics can reduce the incidence of VAP, shorten the duration of mechanical ventilation and ICU stay, and reduce the pathogen load in the sputum of mechanically ventilated patients on the 7th day.

Promoting the transformation of scientific and technological achievements in hospitals can significantly enhance the new productivity levels and innovation capabilities in China's biomedicine sector.However,specialized hospitals face several challenges due to their smaller scale and singular discipline layout.These include insufficient interdisciplinary collaboration,in-adequate funding and capacity to attract funds,a lack of awareness and motivation among hospital staff regarding achievement transformation,limited experience in transforming results,and difficulties in industrializing outcomes.To effectively improve the transformation of scientific and technological achievements,specialized hospitals can adopt strategies such as strengthening the in-tegration of industry,academia,research,and healthcare;increasing financial investment;enhancing theoretical training on a-chievement transformation;building a team of transformation professionals;and exploring diverse pathways for achievement trans-formation.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

This article reviews the clinical studies about the treatment of allergic rhinitis （AR） with traditional Chinese medicine （TCM） in recent years. AR is a common and frequently occurring disease in the department of otolaryngology. The common manifestations of AR include nasal congestion， sneezing， runny nose， and nasal itching. AR， belonging to the category of rhinitis， is a dominant disease in the TCM treatment of otorhinolaryngologic diseases and head and neck diseases. The ancient literature has laid a solid theoretical basis on the etiology and pathogenesis of AR. According to the ancient literature， the theoretical basis， and their own experience， modern doctors classified the causes of AR into the disorders in Zang-fu organs and six meridians. Most of the explanations focus on the disorders in Zang-fu organs， especially the lung， spleen， and kidney. The clinical studies in this field mainly involve TCM treatment alone， integrated TCM and Western medicine treatment， and TCM external treatment. These therapies have good efficacy in the clinical treatment of AR. Among them， TCM treatment alone has significant advantages in alleviating the symptoms and nasal signs， declining the scores of related scales， and reducing the eosinophil count （EOS） of nasal secretions， with definite long-term efficacy. Integrated TCM and Western medicine treatment can complement with each other. The TCM external treatment methods include acupuncture， moxibustion， acupoint catgut embedding， acupoint application， and nasal irrigation with TCM， which are safe， simple， acceptable by patients and have good therapeutic effect. Finally， the clinical research status of TCM treatment of AR was summarized， and suggestions were put forward from three aspects： standardizing the clinical research protocol of TCM， encouraging pure TCM research， and exploring the mechanism of TCM treatment on the basis of frontier research achievements. This review aims to provide higher-level evidence for subsequent clinical research and promote the research on dominant AR diseases.

【Objective】 To investigate the effects of total flavone of oldenlandia diffusa (FOD) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) stem cells sorted from Huh7. 【Methods】 Human HCC cell lines Huh7 was cultured in vitro; CD133 positive (CD133⁺) stem cells in Huh7 cell line were sorted by flow cytometry, and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting. CD133⁺-Huh7 was stimulated by different concentrations (0 μg/mL, 50 μg/mL, 100 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h, 72 h and 96 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on CD133⁺-Huh7 proliferation while Annexin V-PE/7-AAD was used to detect the effect of FOD on CD133⁺-Huh7 apoptosis. Western blotting was used to detect the protein expressions of protein 53 (P53), factor associated suicide-Fas-associating protein with a novel death domain (Fas-FADD), B-cell lymphoma-2 (Bcl-2), Cleaved-Caspase3, and Bcl-2 associated X protein (Bax). 【Results】 More than 95% of stem cells were purified for further experiments. Cell proliferation of CD133⁺-Huh7 was significantly inhibited by FOD, with the significant suppression at the concentration of 100 μg/mL for 72 h compared with negative control group (P<0.05). The apoptosis rate was significantly upregulated than that in the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and Cleaved-Caspae3 increased via FAS/FADDD and P53 axis. 【Conclusion】 FOD can significantly inhibit the proliferation and promote the apoptosis of CD133⁺-Huh7.

Glaucoma is one of blind causing diseases. The cup-to-disc ratio is the main basis for glaucoma screening. Therefore, it is of great significance to precisely segment the optic cup and disc. In this article, an optic cup and disc segmentation model based on the linear attention and dual attention is proposed. Firstly, the region of interest is located and cropped according to the characteristics of the optic disc. Secondly, linear attention residual network-34 (ResNet-34) is introduced as a feature extraction network. Finally, channel and spatial dual attention weights are generated by the linear attention output features, which are used to calibrate feature map in the decoder to obtain the optic cup and disc segmentation image. Experimental results show that the intersection over union of the optic disc and cup in Retinal Image Dataset for Optic Nerve Head Segmentation (DRISHTI-GS) dataset are 0.962 3 and 0.856 4, respectively, and the intersection over union of the optic disc and cup in retinal image database for optic nerve evaluation (RIM-ONE-V3) are 0.956 3 and 0.784 4, respectively. The proposed model is better than the comparison algorithm and has certain medical value in the early screening of glaucoma. In addition, this article uses knowledge distillation technology to generate two smaller models, which is beneficial to apply the models to embedded device.
Humans ; Optic Disk/diagnostic imaging* ; Glaucoma/diagnosis* ; Algorithms ; Diagnostic Techniques, Ophthalmological ; Databases, Factual

Ménière's disease （MD） is an inner ear disease characterized by vertigo， tinnitus， hearing loss， and ear stuffiness. Modern therapies such as drugs， surgery， and vestibular function rehabilitation have limited effects in relieving the symptoms and reducing the recurrence. Traditional Chinese medicine （TCM） can alleviate the symptoms of MD with simple operation and mild adverse reactions while emphasizing psychological adjustment. The TCM treatment of MD is individualized depending on different stages and pathogenic factors. The internal treatment mainly targets phlegm， dampness， water， wind， fire， deficiency， and blood stasis. External interventions include acupuncture and moxibustion. This paper reviewed the published articles about the treatment of MD with TCM. In recent five years， the published studies were mainly clinical trials and experience discussion （or case reports）， and few reports of fundamental research were published. In these studies， the Western medicine diagnosis of MD mostly refers to the Diagnostic Basis and Efficacy Evaluation of Ménière's Disease （Guiyang， 2006） and the Guidelines for Diagnosis and Treatment of Ménière's Disease （2017）， while the TCM diagnosis mostly refers to the Criteria of Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine issued by the National Administration of TCM in 1994. The efficacy was mostly evaluated based on clinical efficacy， scales， syndrome scores， pure tone audiometry， etc.， while caboratory indexes were rarely used. The available clinical studies about the treatment of MD with TCM generally have low quality of evidence and single intervention means. In the future， the research on the treatment of MD with TCM can be improved by standardizing the research program， improving the quality of evidence， exploring more intervention methods， and strengthening basic research.