OBJECTIVES: As early as the Apollo 11 mission, astronauts experienced ocular, skin, and upper airway irritation after lunar dust (LD) was brought into the return cabin, drawing attention to its potential biological toxicity. However, the biological effects of LD exposure through the digestive system remain poorly understood. This study aimed to evaluate the impact of digestive exposure to lunar dust simulant (LDS) on gut microbiota and on the intestine, liver, kidney, lung, and bone in mice. METHODS: Eight-week-old female C57BL/6J mice were used. LDS was used as a substitute for lunar dust, and Shaanxi loess was used as Earth dust (ED). Mice were randomly divided into a phosphate buffered saline (PBS) group, an ED group (500 mg/kg), and a LDS group (500 mg/kg), with assessments at days 7, 14, and 28. Mice were gavaged once every 3 days, with body weight recorded before each gavage. At sacrifice, fecal samples were analyzed by 16S ribosomal RNA (rRNA) sequencing; inflammatory cytokine expression [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] in intestinal, liver, and lung tissues was measured by real-time reverse transcription PCR (real-time RT-PCR); hematoxylin and eosin (HE) staining was performed on lung, liver, and intestinal tissues; Periodic acid-Schiff (PAS) staining was used to assess the integrity of the intestinal mucus barrier, and immunohistochemical staining was performed to evaluate the expression of mucin-2 (MUC2). Serum biochemical tests assessed hepatic and renal function. Femoral bone mass was analyzed by micro-computed tomography (micro-CT); osteoblasts and osteoclasts were assessed by osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow immune cell subsets were analyzed by flow cytometry. RESULTS: At day 10, weight gain was slowed in ED and LDS groups. At days 22 and 28, body weight in both ED and LDS groups was significantly lower than controls (both P<0.05). LDS exposure increased microbial species richness and diversity at day 7. Compared with the PBS and ED groups, mice in the LDS group showed increased relative abundance of Deferribacterota, Desulfobacterota, and Campylobacterota, and decreased Firmicutes, with increased Helicobacter typhlonius and reduced Lactobacillus johnsonii and Lactobacillusmurinus. HE and PAS staining of the colon showed that mucosal structural disruption and goblet cell loss were more severe in the LDS group. In addition, immunohistochemistry revealed a significant downregulation of MUC2 expression in this group (P<0.05). No obvious pathological alterations were observed in liver HE staining among the 3 groups, and none of the groups exhibited notable hepatic or renal dysfunction. HE staining of the lungs in the ED and LDS groups showed increased perivascular inflammatory cell infiltration (both P<0.05). CONCLUSIONS LDS exposure via the digestive route induces gut dysbiosis, intestinal barrier disruption, pulmonary inflammation, bone loss, and bone marrow immune imbalance. These findings indicate that LD exposure poses potential health risks during future lunar missions. Targeted restoration of beneficial gut microbiota may represent a promising strategy to mitigate LD-related health hazards.
Animals ; Dust ; Mice ; Mice, Inbred C57BL ; Dysbiosis/etiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Moon ; Liver/metabolism* ; Digestive System/microbiology* ; Lung/metabolism* ; Kidney

OBJECTIVES: Due to prolonged exposure to cosmic radiation and meteorite impacts, lunar surface dust forms nanoscale angular particles with strong electrostatic adsorption properties. These dust particles pose potential inhalation risks, yet their pulmonary toxicological mechanisms remain unclear. Given the need for dust exposure protection in future lunar base construction and resource development, this study established an acute exposure model using lunar soil simulant (LSS) and used Earth soil (ES; Loess from Shaanxi, China) as a comparison to investigate lung injury mechanisms. METHODS: C57BL/6 mice were randomly assigned to 3 groups: Phosphate buffered saline (PBS), LSS, and ES, with 5 to 7 mice per group. Mice in the LSS and ES groups received a single intratracheal instillation to induce acute inhalation exposure. Body weight was monitored for 28 days. Mice were euthanized at days 3, 7, 14, and 28 post-exposure, and peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. Immune cell subsets in BALF were analyzed using flow cytometry. Hematoxylin-eosin (HE) staining assessed lung structure and inflammation; periodic acid-Schiff (PAS) staining evaluated airway mucus secretion; Masson staining examined collagen deposition. Real-time reverse transcription PCR (real-time RT-PCR) was used to measure the mRNA expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and epithelial barrier genes (Occludin, Cadherin-1, and Zo-1). Lung tissues at day 7 were subjected to transcriptomic sequencing, followed by immune infiltration and pathway enrichment analyses to determine immunoregulatory mechanisms. RESULTS: Body weight in the ES group progressively declined after day 18 (all P<0.05), while the LSS group showed no significant changes compared with the control group. HE staining showed both LSS and ES induced inflammatory cell infiltration around airways and vasculature, which persisted for 28 days but gradually lessened over time. PAS staining revealed marked mucus hypersecretion in the LSS group at day 3, followed by gradual recovery; no significant mucus changes were observed in the ES group. Masson staining indicated no obvious pulmonary fibrosis in either group within 28 days. Real-time RT-PCR demonstrated significant upregulation of IL-1β and TNF-α in both LSS and ES groups, peaking on day 7, accompanied by downregulation of epithelial barrier genes (Occludin, Cadherin-1, and Zo-1)(all P<0.05). Transcriptomic analysis showed that both LSS and ES activated chemokine-related pathways and enriched leukocyte migration and neutrophil recruitment pathways. Further validation revealed upregulation of CXCL2 and MMP12 in the LSS group, whereas CXCL3 and MMP12 were predominantly elevated in the ES group. CONCLUSIONS Both LSS and ES can induce sustained lung injury and neutrophil infiltration in mice, though the underlying molecular mechanisms differ. Compared with ES, exposure to LSS additionally triggers a transient eosinophilic response, suggesting that lunar dust particles possess stronger immunostimulatory potential and higher biological toxicity.
Animals ; Mice ; Mice, Inbred C57BL ; Soil ; Lung Injury/etiology* ; Dust ; Bronchoalveolar Lavage Fluid ; Moon ; Lung/pathology* ; Inhalation Exposure/adverse effects* ; Male

Phase Ⅰ clinical trials play a crucial role in the research and development of new drugs, serving as the initial studies to assess their safety, tolerability, effectiveness, and pharmacokinetic properties in humans. These trials involve uncertainties regarding safety and efficacy. Comprehensive management of all aspects of phase Ⅰ clinical trials for anti-tumor drugs is crucial to protect the rights and safety of participants. This article provides an in-depth analysis of the key points and precautions necessary for effective quality control throughout the process. The analysis is informed by guidelines such as the “Good Clinical Practice for Drugs” “Key Points and Judgment Principles for Drug Registration Verification” “Key Points and Judgment Principles for Supervision and Inspection of Drug Clinical Trial Institutions” and the standard operating procedures for quality control of the center. Topics discussed include informed consent, inclusion criteria, experimental drugs, biological samples, adverse events, and serious adverse events. The goal is to standardize quality control in phase Ⅰ clinical trials of anti-tumor drugs, ensure the authenticity and reliability of clinical trial data, and protect the rights and safety of participants.

To implement the instructions and directives of General Secretary Xi Jinping on important documents related to traditional Chinese medicine （TCM）， adhere to the equal emphasis on TCM and Western medicine， and promote mutual complementarity， win-win cooperation， and coordinated development between TCM and Western medicine， the China Association of Chinese Medicine has organized seminars on the clinical dominant diseases of TCM in multiple professional fields， achieving a series of results. The aim is to implement the research on dominant diseases of TCM described in the Law of the People's Republic of China on Traditional Chinese Medicine and the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance， Innovation and Development of Traditional Chinese Medicine， thus serving the construction of advantageous specialties， clinical talent cultivation， national scientific and technological layout， and academic innovation leadership. In the field of otolaryngology， the China Association of Chinese Medicine and many Chinese and Western medicine experts across the country have conducted multiple in-depth discussions and research. At the 10^th Clinical Dominant Disease Series Youth Salon， they have elaborated and demonstrated the basic and specific suggestions and consensus on the clinical advantages of TCM and integrated TCM and Western medicine in the treatment of allergic rhinitis （AR）， making great progress. However， there is still a lack of detailed research paths. Under the guidance of the China Association of Chinese Medicine and based on the TCM Dominant Disease Series Salon for AR， this study analyzed the difficulties encountered in AR diagnosis and treatment according to the occurrence and development law of AR. Based on the advantages and characteristics of AR diagnosis and treatment by TCM and integrated TCM and Western medicine， it explored the research paradigm and technological layout points of AR and put forward suggestions. The layout involved four aspects： Optimization of the AR diagnosis and treatment system， prevention and control of comorbidities， management of chronic diseases， and a platform for TCM inheritance. Additionally， suggestions for layout and research directions， expected goals and values， and priority levels for funding were proposed. The study is expected to provide a theoretical basis and development ideas for the future prevention and treatment of AR with TCM and integrated TCM and Western medicine and promote the high-quality development of TCM.

Objective: To examine the causal relationship between endometrial cancer and breast cancer using bidirectional two-sample Mendelian randomization (MR) approach. Methods: Genetic association data of endometrial cancer were collected through a meta analysis, including 54 884 participants and 9 464 330 single nucleotide polymorphisms (SNPs), and genetic association data of breast cancer were collected through the Breast Cancer Society Consortium, with 228 951 participants and 10 680 257 SNPs. A forward MR analysis was performed using the inverse variance weighted (IVW) method with 8 endometrial cancer-associated SNPs as instrumental variables and breast cancer as the study outcome, and a reverse MR analysis was performed with 112 breast cancer-associated SNPs as instrumental variables and endometrial cancer as the study outcome. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression, and the robustness of the results was verified with the leave-one-out. Results: Forward MR analysis results showed that patients with genetically predicted endometrial cancer had an increased risk of breast cancer compared to those without endometrial cancer (OR=1.083, 95%CI: 1.037-1.132). Reverse MR analysis showed that patients with genetically predicted breast cancer had an increased risk of endometrial cancer compared to those without breast cancer (OR=1.070, 95%CI: 1.010-1.134). Cochran's Q test detected no heterogeneity (P>0.05), and neither the MR-PRESSO test nor the MR-Egger regression revealed horizontal pleiotropy of instrumental variables (both P>0.05). Leave-one-out analysis showed robustness of the MR analysis results. Conclusion There are bidirectional causal relationship between endometrial cancer and breast cancer.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled

Objective:To explore the effects of Onodera′s prognostic nutritional index (PNI) on the prognosis of locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC) after induction chemotherapy followed by sequential chemoradiotherapy.Methods:A retrospective analysis was conducted on the clinical data of 52 LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy in The Affiliated Cancer Hospital of Guizhou Medical University during 2014-2018. The PNI values of all the patients at different treatment phases were statistically analyzed, and the ROC curve was employed to determine the optimal critical value of PNI. The patients in this study were divided into a well-nourished group ( n = 27) and a poorly-nourished group ( n = 25). The Kaplan-Meier method was used for survival analysis. The Cox proportional hazards model was utilized to analyze the relationships between different nutritional status and prognosis. Clinical features and adverse reactions were compared between the two groups. Results:The PNI values decreased significantly after radiotherapy, with an optimal critical value of 42.4. The 5-year overall survival (OS) and progression-free survival (PFS) of the well-nourished group (PNI ≥ 42.4) were 62.6% and 60.9%, respectively, which were significantly higher than those (30.1% and 29.7%) of the poorly-nourished group (PNI < 42.4, χ2 = 11.12, 5.74, P < 0.05). The multivariate analysis showed that PNI was an independent prognostic factor for the OS after radiotherapy ( HR = 2.752, 95% CI: 1.095-6.917, P = 0.031). The LA-OPSCC patients aged over 60 years or those who did not respond to induction chemotherapy accounted for a higher proportion of malnutrition after chemoradiotherapy ( χ2 = 4.89, 5.05, P < 0.05). Conclusions:PNI after radiotherapy can be used as a prognostic factor in the evaluation of LA-OPSCC patients receiving induction chemotherapy followed by sequential chemoradiotherapy. The LA-OPSCC patients aged over 60 years or those who do not respond to induction chemotherapy should receive more nutritional support during the chemoradiotherapy.

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 explore the clinical significance and prognostic value of fibrinogen (FIB) in the treatment of locally advanced head and neck squamous cell carcinoma with induction chemotherapy combined with radiotherapy.Methods:A retrospective analysis was conducted for the clinical data of 114 patients with locally advanced head and neck squamous cell carcinoma receiving non-surgical treatment in the Department of Head and Neck Oncology, the Affiliated Cancer Hospital of Guizhou Medical University from May 2011 to May 2021. The FIB critical value was determined based on the median FIB level before induction chemotherapy, by which patients were divided into high-FIB and low-FIB groups. The ROC curves were used to determine the optimal cut-off value for other hematologic-related parameters such as neutrophils, lymphocytes, and platelets. Statistical methods were used to analyze the results. The enumeration data were analyzed by Chi-square test or Fisher exact probability method. Survival curves for OS and PFS were plotted by Kalplan-Meier method and tested by Log-rank method. Prognostic factors were evaluated by Cox proportional hazard regression model.Results:There were 59 cases in the high-FIB group (FIB > 3.6 g/L) and 55 cases in the low-FIB group (FIB ≤ 3.6 g/L). The high FIB group had higher neutrophils, platelets, NLR, and PLR ( χ2= 7.84, 12.80, 15.04, 9.14; P<0.05) than the low FIB group. The 3- and 5-year overall survival (OS) rates were significantly longer in the low FIB group than those in the high-FIB group (62.9% vs. 39.6%; 46.9% vs. 25.8%), and progression-free survival (PFS) rates of the low FIB group significantly longer than those of the high-FIB group (63.3% vs. 40.3%; 48.1% vs. 26.2%). The univariate analysis showed that the OS and PFS in patients with locally advanced head and neck squamous cell carcinoma were related to FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes. The multivariate analysis showed that FIB, the application of concurrent chemoradiotherapy, and the efficacy of radiotherapy for lymph nodes were independent prognostic factors of the OS [ HR (95% CI): 1.89 (1.08-3.31), 3.76 (1.12-12.65), 2.14 (1.09-4.21), P < 0.05]and PFS HR (95% CI): 1.92 (1.90-3.36), 3.93 (1.01-11.34), 2.15 (1.09-4.22), P < 0.05]of patients with locally advanced head and neck squamous cell carcinoma. Conclusions:Patients with low FIB receive high OS and PFS rates after induction chemotherapy combined with radiotherapy. Therefore, FIB can be used as a prognostic factor in the evaluation of non-surgical treatment of patients with locally advanced head and neck squamous cell carcinoma.