ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Tracheobronchial adenoid cystic carcinoma （TACC） is a low-grade malignant tumor originating from the airway mucosa. Despite its slow progression，it is characterized by high invasiveness，frequent recurrence，and a strong tendency for metastasis. Preclinical studies have shown that vascular-targeted therapy holds significant potential. However，an effective systemic treatment for TACC has not been established yet. This study explored TACC from the perspective of "Feiji" in traditional Chinese medicine （TCM） as the starting point. It deeply investigated the mechanisms of abnormal collaterals and tumor vascular recruitment and further elaborated on the theoretical connection between abnormal collaterals and tumor vascular recruitment. Firstly，collateral hyperactivity led to disordered and erratic pulmonary collaterals. Their abnormal structures were similar to the disorderly and tortuous nature of tumor （pseudo）angiogenesis. This resulted in imbalances in the functions of circulation，perfusion，and reverse injection of the pulmonary collaterals，and then led to unrestrained collateral dysfunction and the accumulation of pathogenic factors. Secondly，the remodeling of the extracellular matrix （ECM） and epithelial-mesenchymal transition （EMT） in TACC were critical processes in vascular co-option （VCO），representing the micro-level manifestation of the displacement of nutrient and defense. During this process，ECM remodeling made TACC cells more likely to hijack normal blood vessels，creating a complex vascular microenvironment conducive to tumor growth. In terms of treatment，this study proposed a TCM strategy of "regulating collaterals to expel pathogenic factors and nourishing collaterals to strengthen the healthy Qi"，and listed potential TCM. These were intended to regulate the Qi and blood in the collaterals，repair the functions of abnormal collaterals，and intervene in the vascular recruitment process of TACC. Future research should focus on improving the TCM clinical syndrome characteristics of TACC. Through modern molecular biology techniques，it is necessary to deeply analyze the micro-level pattern of vascular recruitment in TACC. This would enrich the understanding of the profound connection between abnormal collaterals and tumor vascular recruitment，providing empirical evidence for TCM-targeted therapies for vascular recruitment in TACC.

In recent years, China has been facing the dual challenges of declining fertility rates and births, with male reproductive health issues, especially the decline in semen quality, identified as a pivotal contributor to this phenomenon. Meanwhile, accumulating evidence indicates that air pollutants, an increasingly severe environmental problem, can damage semen quality not only directly through their biological toxicity but also indirectly by disrupting the composition of microbial communities in the gut and semen, thereby dysregulating immune function, endocrine homeostasis, and oxidative stress responses. The gut microbiota and semen microbiota, as important components of the human microecosystem, play crucial roles in maintaining reproductive health. This article comprehensively reviewed the research progress on the potential effects of air pollutants (particulate matter and gaseous pollutants), gut microbiota, and semen microbiota on semen quality. Specifically, it elucidated the mechanisms of interaction between these factors and explored how they affect male fertility.

Background Deoxynivalenol (DON), a priority contaminant for food safety risk monitoring, is produced by Fusarium spp. infesting crops, and its common derivatives are 3-acetyl-DON (3A-DON) and 15-acetyl-DON (15A-DON), which have been shown to possess gastrointestinal toxicity, immunotoxicity, reproductive toxicity, and cytotoxicity. Due to the stable physicochemical properties of the DON family of toxins (DONs), they cannot be effectively removed during food processing, thus following the food chain, entering the human body, and posing health risks. Objective To understand the contamination status of DONs in commercial foods (cereals and bakery products) in Shanghai in 2022–2023, and to assess the exposure risk of DONs in pregnant women by combining their dietary consumption data. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determine the contamination level of DONs in 1 100 food samples (cereals and baked goods) collected in 2022 and 944 samples collected in 2023 from Shanghai. The dietary monitoring data of pregnant women in Shanghai from 2016 to 2017 were adopted. The monitoring employed the food frequency questionnaire distributed among pregnant women through a combination of online telephone enquiry and offline on-site face-to-face survey to estimate their food consumption levels. An exposure assessment model was established to calculate the exposure level to DONs, and the probability distribution of the DONs exposure level in the pregnant women group in Shanghai was obtained by applying @Risk 7.5 software and simulating the calculation according to the Monte Carlo principle. With reference to the tolerable daily intake (TDI) of DONs [1.00 µg·(kg·d)⁻¹] proposed by the Joint FAO/WHO Expert Committee on Food Additives, the risk of exposure to DONs from commercial cereals and bakery products in pregnant women in Shanghai was assessed. Results DONs were detected in cereal and bakery samples collected in 2022 and 2023 with different levels of contamination. The level of DONs in cereal foods in 2023 (mean: 36.33 µg·kg⁻¹) decreased compared to 2022 (mean: 23.64 µg·kg⁻¹). However, the positive rate (71.67%) and level (mean: 51.22 µg·kg⁻¹) of DONs in bakery products increased significantly compared with 2022 (positive rate: 10.00%, mean: 24.39 µg·kg⁻¹). The mean consumption of cereals in 783 pregnant women was 222.48 g·d⁻¹ and the mean consumption of bakery products was 36.07 g·d⁻¹, and there was no statistically significant difference in the intake of all types of cereals and bakery products across the early, middle, and late stages of pregnancy. The modelled intakes of DONs via commercial cereals and bakery products for pregnant women in Shanghai were calculated to be 0.20 and 0.57 µg·(kg·d)⁻¹ in 2022 for the mean level and the 95th percentile level, respectively, and 0.16 µg·(kg·d)⁻¹ and 0.35 µg·(kg·d)⁻¹ in 2023, respectively. The results of the health risk assessment showed that pregnant women in Shanghai had 2.6% and 1.4% probability of exposure to DONs from cereal consumption in 2022 and 2023, respectively. Conclusion The risk of exposure of pregnant women in Shanghai to DONs via commercial cereals and bakery products is relatively low (1.4%-2.6%). However, considering the physical sensitivity of pregnant women, they should avoid consuming moldy grains and appropriately reduce intake of bakery products.

Objective To explore the prognostic value and immune infiltration landscape of anoikis-related long noncoding RNAs (arlncRNAs) in lung adenocarcinoma. Methods RNA-seq and clinical data of lung adenocarcinoma were downloaded from the TCGA database, and anoikis-related genes were obtained from the GeneCards and Harmonizome databases. Coexpression, differential, and WGCNA analyses were performed to screen differentially expressed arlncRNAs closely related to the occurrence of lung adenocarcinoma. A prognostic risk model was then constructed based on the arlncRNAs, and its predictive efficacy was further validated. Finally, consensus clustering was used to identify the molecular subtypes associated with anoikis in lung adenocarcinoma. Results Seven prognostic arlncRNAs were identified, and the prognostic risk models established based on them had AUC values of ROC curves greater than 0.7. Survival and immune infiltration analyses revealed that low-risk patients had high overall survival and immune infiltration, implying that they experienced good immune treatment effects. Drug sensitivity analysis showed that the high-risk patients were more sensitive to commonly used chemotherapeutic agents than the low-risk patients. According to the expression of model genes, subtypes C1 and C2 were identified through consensus clustering, and C1 showed a good prognosis. Conclusion The prognostic risk model based on the seven arlncRNAs can effectively predict the prognosis of lung adenocarcinoma patients. The results of immune-related and drug sensitivity analyses provide a reference for the precise individualized treatment of patients with lung adenocarcinoma.

The expression level of NOD-like receptors(NLRP3)inflammasome is significantly elevated in breast cancer tissues,and a high level of NLRP3 inflammasomes is closely associated with breast cancer metastasis.Activation of NLRP3 inflammasome can induce the release of inflammatory factors into the tumor microenvironment(TME).These inflammatory factors,by signaling to cancer cells,reshape the TME to promote tumor growth and invasion,ultimately facilitating the process of epithelial-mesenchymal transition.This equips cancer cells with the ability to establish distant metastases and increase the formation of metastatic lesions.This review addresses the current research status and prospects of NLRP3 inflammasomes in the breast cancer TME and their role in breast cancer metastasis.The goal is to provide new insights for the study of breast cancer metastasis mechanisms and treatment strategies.

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

ObjectiveTo explore the possible mechanism of Bimin Formula （鼻敏方） in treating lung-spleen qi deficiency syndrome of allergic rhinitis （AR） with high mucin secretion. MethodsThirty-four SD rats were randomly divided into a blank group （8 rats）， a model group （8 rats）， a low-dose Bimin Formula group （8 rats）， and a high-dose Bimin Formula group （10 rats）. Except for the blank group， the other groups were subjected to AR lung-spleen qi deficiency rat models induced by smoking， gavage of Ginkgo biloba leaf extract， and ovalbumin. After modeling， rats in the low- and high-dose Bimin Formula groups were given Bimin Formula concentrate （concentration of 2.16 g/ml） by gavage at doses of 1.08 g/100 g and 2.16 g/100 g， respectively， while rats in the model group were given 0.5 ml/100 g of normal saline by gavage， once daily for 28 days； the blank group was not intervened. Behavioral assessments were performed after intervention. ELISA was used to detect the levels of peripheral blood total immunoglobulin E （IgE）. HE staining was used to observe the pathological changes of nasal mucosa epithelium in rats， while immunohistochemistry was used to detect the expression of transmembrane protein 16A （TMEM16A） and mucin 5AC （MUC5AC） protein in nasal mucosa. Western Blot was used to detect the expression of nuclear factor kappa B （NF-κB） protein， and RT-PCR was used to detect the expression of TMEM16A， MUC5AC， and NF-κB mRNA in nasal mucosa. ResultsHE staining showed that the nasal mucosa epithelial cell structure in the blank group was intact without shedding， swelling， or necrosis； the nasal mucosa epithelial tissue of rats in the model group was thickened and partially shed， with infiltration of eosinophils and lymphocytes visible； the pathological changes in nasal mucosa tissue of rats in the high- and low-dose Bimin Formulagroups were improved， and more improvement was showen in the high-dose group. Compared with those in the blank group， the behavioral scores and peripheral blood total IgE levels of rats in the model group significantly increased， as well as the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosa （P＜0.05 or P＜0.01）. Compared with those in the model group， the behavioral scores and peripheral blood total IgE levels of rats in the high-dose Bimin Formula group decreased， and the expression of TMEM16A， MUC5AC， and NF-κB proteins and mRNA in nasal mucosaalso decreased （P＜0.05 or P＜0.01）； the behavioral scores and peripheral blood total IgE levels of rats in the low-dose Bimin Formula group were reduced， and the expression of TMEM16A and MUC5AC proteins and mRNA in nasal mucosa， as well as the expression of NF-κB protein decreased （P＜0.05 or P＜0.01）， but the difference in NF-κB mRNA expression was not statistically significant （P＞0.05）. Compared with the low-dose Bimin Formula group， the expression of NF-κB protein in the high-dose group decreased （P＜0.01）. ConclusionBimin Formula may improve the symptoms and high mucus secretion of AR lung-spleen qi deficiency by regulating the TMEM16A/NF-κB/MUC5AC signaling pathway in nasalmucosa.

With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.