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

Objective To compare the lipid-lowering efficacy and safety of fixed-dose combination and free combination of rosuvastatin and ezetimibe in hypercholesterolemia patients who fail to achieve low-density lipoprotein cholesterol(LDL-C)goal with statin monotherapy.Methods A total of 45 hypercholesterolemia patients who switched from statin monotherapy to fixed-dose combination of rosuvastatin and ezetimibe after failing to achieve target LDL-C goal admitted at cardiological departments of First Affiliated Hospital of Sun Yat-sen University,Nanhai Fourth People's Hospital,Foshan First People's Hospital,and Guangdong Provincial People's Hospital between March and June 2024 were enrolled and served as the study group.Another 120 hyper-cholesterolemia patients who treated with free combination of rosuvastatin and ezetimibe were se-lected from Xiamen Regional Health Medical Big Data Platform with propensity score matching and served as control group.The LDL-C level,LDL-C reduction,and changes in TC,HDL-C and TG levels in 4-6 weeks after the medication switch,as well as the safety indicators(AST,ALT,CK,Cre and eGFR)were compared between the two groups.Results In 4-6 weeks after the medication switch,the patients in the study group exhibited a significant decrease in LDL-C level(1.70±0.44 mmol/L vs 2.12±0.87 mmol/L,P＜0.01),obvious LDL-C reduction[(43.17±16.11)％vs(29.14±29.13)％,P＜0.01]when compared to those of the control group.The LDL-C goal attainment rate was significantly higher in the study group than the control group(71.11％vs 45.00％,P=0.003).In addition,there were no statistical differences in the levels of HDL-C and TG and the reductions of HDL-C and TG between the two groups in 4-6 weeks after treatment(P＞0.05).The study group obtained notably lower TC level and TC reduction than the control group in the time(P＜/0.05,P＜0.01).After treatment,no statistical differences were observed between the two groups in terms of AST,ALT,CK,Cre and eGFR(P＞0.05).Conclusion Com-pared to free combination of rosuvastatin and ezetimibe,fixed-dose combination can further reduce LDL-C level in hypercholesterolemia patients who have not achieved LDL-C goal with statin monotherapy,with higher LDL-C goal attainment rate and good safety.

Objective:To summarize the clinical phenotype and genetic characteristics of Poirier-Bienvenu neurodevelopmental syndrome associated with CSNK2B gene variation. Methods:The clinical and genetic data of a child with Poirier-Bienvenu neurodevelopmental syndrome caused by shear variant of CSNK2B gene who was diagnosed in the Department of Neurology, Children′s Hospital Affiliated to Zhengzhou University in March 2022 were collected. Previous relevant literature at home and abroad was reviewed to summarize the clinical characteristics of the disease. Results:The child was a girl aged 13 months, mainly due to "intermittent convulsions for 2 months" for consultation. The clinical manifestations of the girl were normal face, generalized tonic-clonic seizures, low intelligence, language and motor retardation, and there was no abnormality in the long-range video electroencephalography and the head magnetic resonance imaging. No abnormality was found in chromosome karyotype analysis and chromosome coefficient of copy variation analysis. The whole exon gene sequencing test indicated that the child carried de novo heterozygous shear variant of CSNK2B gene c.291+5G>C, which had not been reported in the literature. According to the clinical manifestations and genetic examination results of the child, the diagnosis of Poirier-Bienvenu neurodevelopmental syndrome was clear. The CSNK2B gene of the proband′s parents and the twin sister was wild-type. The application of sodium valproate anti-seizure medication could effectively control the seizures of the child, and by giving rehabilitation function training, the child′s language and gross motor function was improved. Conclusions:The Poirier-Bienvenu neurodevelopmental syndrome is a rare autosomal dominant disorder caused by variants in the CSNK2B gene. The clinical manifestations are infancy-onset seizures, intellectual development disorders, language and motor development disorders, etc, and the video electroencephalogram and skull magnetic resonance are mostly normal. The CSNK2B gene shear variant is the genetic etiology of the proband.

Objective:To evaluate the use of ulthera in carotid body tumor resectionMethods:From Jun 2004 to Jun 2019 at the First Hospital of China Medical University. Forty-three shamblin grade Ⅱ or Ⅲ patients were retrospectively assigned to ulthera assisted carotid body tumor resection (26 cases) and traditional carotid body tumor resection (17 cases).Results:In ulthera assisted group, the average tumor diameter was (4.0±0.6) cm, compared to (3.9±0.9) cm in traditional carotid body tumor surgery group, P=0.875. The operation time of the two group was respectively (117.6±39.8) min and (149.4±55.0) min ( P=0.005), blood loss (145.7±70.6) ml vs. (194.1±80.7) ml ( P=0.006), hospital stay was (16.8±7.5) d vs. (22.7±13.0) d ( P=0.017), and following-up period was between 6 and 180 months. One patient relapsed in ulthera assisted group. The postoperative complications occurred in 8 and 7 cases respectively. Conclusion:Ulthera assisted carotid body tumor resection helps shorten operation time, hospital stay and decrease intraoperative blood loss.

Objective:To explore the incidence, clinical characteristics and prognosis of invasive pulmonary fungal infection(IPFI)in recipients of lung transplantation(LT)in southern China.Methods:From January 2003 to August 2019, retrospective analysis was performed for 300 recipients of lung transplantation at three hospitals in southern China. There were 254 males and 46 females with an average age of (54.98±14.2)years. Clinical data were collected from medical records, including symptoms and signs, imaging studies, bronchoscopy examination, pathogen separation and culture from deep sputum and bronchoalveolar lavage fluid(BALF), fungal-related laboratory tests and tissue pathology.Results:Among 300 cases, 93(31.0%)had at least one episode of IPFI. The most common pathogen was aspergillosis(60.2%), followed by candida(15 cases, 16.1%)and Pneumocystis jeroveci (13 cases, 14.0%). Kaplan Meier analysis indicated that all-cause mortality was significantly higher in IPFI group than that in non-IPFI(nIPFI)group with one-year mortality of 45.2% vs. 26.7% in IPFI and nIPFI groups respectively( P<0.05). Conclusions:IPFI is prevalent after LT in southern China. And aspergillosis is the most common pathogen and Candida comes the next. The median occurring time for aspergillosis is 6 months after LT. Candida infection occurs earlier at airway anastomosis. A higher incidence of invasive fungal disease(IFD)associated with a lower survival indicates that IPFI has a substantial mortality among recipients after LT. Prophylactic agents should be optimized based upon an epidemiologically likely pathogen.

Objective To explore the feasibility of a high-resolution melting(HRM)method for rapid screening of SLC4A1 mutation.Methods Two hereditary spherocytosis(HS)with a c.166A >G heterozygous mutation of SLC4A1 confirmed by DNA sequencing and thirty healthy controls were selected for the study.The HRM primer was designed by Primer Premier 6.0 software.All of these samples were detected by LightCycler?480 and analyzed by HRM.Results The HRM analysis was able to detect the c.166A>G heterozygous mutation of SLC4A1 effectively, and the specificity and sensitivity were both 100%.Conclusions The HRM analysis was appropriate for the detection of c.166A>G in SLC4A1.It was an efficient,accurate and cost-effective molecular diagnosis method.

Objective To explore the selection of medical unit and the major influencing factors among residents in Hubei province,to allocate reasonably the health resources and provide reference for developing medical policy.Methods With the method of multi-stage stratified cluster sampling,household survey were done.The multilevel statistical model was used to analyze the influencing factors of the first diagnosed agencies.Results The proportions of residents who chose primary medical institutions as the first diagnosed agencies were 64.5％ in urban areas and 84.3％ in rural areas,and the visiting rate decreased as the level of health care institutions increased.The selection of first diagnosed agencies among patients were related to district (city or village,OR=0.463,95％CI..0.254-0.842),age (OR=1.023,95％CI:1.010-1.036),the educational attainment (OR＞1.000),illness duration in days (OR=0.945,95％CI:0.917-0.973) and number of days in bed (OR=0.854,95 ％ CI:0.825-0.884).Conclusion The residents who chose primary medical institutions as the first diagnosed agencies took a large proportion.District,age,the educational attainment and the illness duration in days had influence on the selection of the first diagnosed agencies among residents.

Objective To discuss the clinical application of percutaneous radiologic gastrostomy (PRG) in treating dysphagia associated with amyotrophic lateral sclerosis (ALS),and to evaluate its safety and improvement effect on patient's nutritional status in ALS patients with pulmonary insufficiency.Methods The clinical data of 51 ALS patients who received PRG were retrospectively analyzed.The success rate of surgery and postoperative complications were recorded.All patients were regularly followed up,and the longterm complications as well as the one-,3-and 6-month mortality rates after the surgery were documented.The improvement of patient's nutritional status was evaluated.Results PRG was successfully accomplished in all 51 patients,the technical success rate was 100％.Mild postoperative complications occurred in 7 patients (13.73％) and severe massive hemorrhage in one patient (2.0％).After PRG,no signs or symptoms of impaired respiratory function were observed.No death occurred in one month and in 3 months after PRG.Six months after PRG,three patients died(6.8 ％,3/44).One month after PRG,31 patients had an increase in body weight of more than 1 kg,and the mean BMI was increased from preoperative t8.60±2.14 to postoperative 19.27±1.81 (one month after PRG),19.17±1.93 (3 month after PRG) and 18.89±2.33 (6 month after PRG).Conclusion For the performance of PRG no gastroscopy or anesthesia is needed,thus,the risk of aspiration asphyxia can be reduced in ALS patients complicated by pulmonary insufficiency and the success rate as well as the safety can be improved.Therefore,this technique is an effective means to ensure that the ALS patients with pulmonary insufficiency can get adequate energy intake to improve their nutritional status.

Objective To understand the worry situation about ill consequences in cancer patients and its relationship with depression.Methods The inpatients with cancer were extracted from 4 general hospitals of Wuhan and Beijing city by the cluster sampling.The self-designed questionnaires were adopted to survey the worry situation about ill consequences in cancer patients.The self-rating depression scale (SDS) was used to assess the patients' depression status.Results A total of 485 cancer patients were surveyed,including 204 males (42.1 ％),281 females(57.9 ％),and the mean age was (56.59 ± 11.19)years old.More than half of the patients usually or always worried about medical expenses.Worries about not taking care of their children,losing their lives,physical disability,leaving sequela and losing life ability also happened a lot.Patients worried more about losing their life,the possibility appearing depression was greater (P＜0.05).The younger the patients were,the greater the depression possibility was;the company staffs had lower risk of depression compared with those whose occupation was others (P＜0.05).Conclusion Cancer patients have different degrees of worries about ill consequences such as medical expenses,not taking care of their children and losing their lives and their worries about losing their lives could affect their depression status.