OBJECTIVE To investigate the efficacy and safety of ropivacaine combined with oxycodone for the analgesia of iliac fascia nerve block in patients undergoing hip replacement. METHODS Sixty-six patients who underwent hip replacement at the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from October 2023 to April 2024 were selected and randomly divided into observation group and control group， with 33 cases in each group. Before induction of anesthesia， ultrasound-guided iliac fascial nerve block was performed. Patients in the observation group were treated with 0.33% ropivacaine+0.1 mg/kg oxycodone injection mixture 30 mL， and patients in the control group were treated with 0.33% ropivacaine injection 30 mL. The time of first postoperative rescue analgesia， 24 h postoperative analgesic drug consumption， sensory block and motor block effective and maintenance time， satisfaction degree， numerical rating scale （NRS） pain score， Ramsay sedation score， muscle strength score， heart rate （HR）， mean arterial pressure （MAP）， oxygen saturation（SpO2）， sleep score， anxiety score， and the occurrence of adverse reactions in the two groups were all recorded. RESULTS Compared with the control group， the first rescue analgesia time after operation was significantly prolonged in the observation group， and 24 h postoperative analgesic drug consumption after operation decreased； the effective time of sensory block was significantly shortened， and the maintenance time of sensory block was significantly prolonged， and the satisfaction score was higher； the NRS pain score after iliac fascia nerve block was lower， HR and MAP were lower， and the anxiety score and sleep score 24 and 48 h after operation were lower （P＜0.05）. In terms of safety， patients in both groups had adverse reactions after operation， such as hypertension， nausea， vomiting， and dizziness， but there was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS Oxycodone combined with ropivacaine shows good efficacy and safety for iliac fascial nerve block analgesia in patients undergoing hip replacement， can significantly prolong the analgesic time of ropivacaine， reduce postoperative analgesic drug consumption， improve the sleep quality of patients， and promote the rapid recovery of patients.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

With the main pathological features of glomerulosclerosis and interstitial fibrosis， renal fibrosis is a key pathological process causing chronic kidney disease to progress to end-stage disease. As a cellular autophagic process， mitochondrial autophagy plays a crucial role in maintaining mitochondrial mass and functional stability. Mitochondrial dysfunction is considered to be one of the key factors driving the progression of fibrosis. Phosphatase and tension protein homologue （PTEN） induce various signalling pathways such as putative kinase 1/parkin， Nip3-like protein X/Bcl-2 interacting protein 3， and FUN14 structural domain-containing protein 1 to activate mitochondrial autophagy to participate in the regulation of fibrogenic factors， amelioration of oxidative stress， and inhibition of inflammatory response and apoptosis， which in turn effectively slows down the progression of renal fibrosis. Studies have shown that traditional Chinese medicine monomers and compound preparations， including phenolics， terpenoids， ketones， and alkaloids， can regulate mitochondrial autophagy-related signalling pathways and achieve significant clinical efficacy in intervening in the progression of renal fibrosis for the treatment of chronic kidney disease. This paper summarized the mechanism of mitochondrial autophagy and the research progress of traditional Chinese medicine intervention in renal fibrosis to provide new ideas for the study of the mechanism of traditional Chinese medicine in treating renal fibrosis.

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

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

Objective:To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province.Methods:Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty.Results:A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (a OR=1.55,95% CI: 1.07-2.25, P=0.019). In island area, older age (60-74 years:a OR=2.52,95% CI: 1.56-4.13; ≥75 years:a OR=11.65,95% CI:5.38-26.70), being women (a OR=1.94,95% CI: 1.20-3.17), suffering from depression (a OR=1.09,95% CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: a OR=1.74,95% CI:1.04-2.94;≥75 years: a OR=4.78,95% CI:2.45-9.50). Polydrug use (a OR=2.08,95% CI: 1.14-3.80) and suffering from depression (a OR=1.10,95% CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: a OR=0.40,95% CI: 0.21-0.75; senior high school and technical secondary school: a OR=0.29,95% CI: 0.15-0.53; college or above:a OR=0.22,95% CI: 0.11-0.42). Conclusions:The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.

Objective To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism.Methods SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes,and histological changes of the thoracic aorta were evaluated using HE staining.In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings,the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine(NE)-and KCl-induced constriction.The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester,indomethacin,zinc protoporphyrin Ⅸ,tetraethyl ammonium chloride,glibenclamide,barium chloride,Iberiotoxin,4-aminopyridine,or TASK-1-IN-1.The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release.Results Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology.While not obviously affecting resting aortic rings with intact endothelium,asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE,but its effects differed between endothelium-intact and endothelium-denuded rings.In endothelium-intact aortic rings pretreated with indomethacin,ZnPP Ⅸ,barium chloride,glyburide,TASK-1-IN-1 and 4-aminopyridine,asiaticoside did not produce significant effect on NE-induced vasoconstriction,and tetraethylammonium,Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside.In KCl-and NE-treated rings,asiaticoside obviously inhibited CaCl2-induced vascular contraction.Conclusion Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening,promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow,thereby reducing systolic blood pressure in rats.

AIM: To investigate the mechanism by which Yijing Decoction antagonist high glucose-induced damage to the basement membrane(BM)in an in vitro inner blood-retinal barrier(iBRB)model.METHODS:Rat retinal microvascular pericytes(RMPs)and endothelial cells(ECs)were isolated and cultured to establish an in vitro iBRB model. The cells were randomly divided into four groups: low glucose group(LG), high glucose group(HG), minocycline group(MG)and Yijing Decoction group(YG). The LG group received 25 mmol/L glucose, the HG group received 60 mmol/L glucose, the MG group received 60 mmol/L glucose + 10 μg/mL minocycline, and the YG group received 60 mmol/L glucose + 10% Yijing Decoction-containing serum. Incubation for each group were terminated after intervention for 12 h. Next, the Western blot analysis was performed to assess the protein expression of BM-related proteins, including collagen Ⅳ(CⅣ)and laminin(LN), as well as matrix metalloproteinase(MMPs)/tissue inhibitor of matrix metalloproteinases(TIMPs)such as MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2.RESULTS:Compared to the LG group, the protein expressions of CⅣ increased in the HG, MG, and YG groups, as did LN in the HG and MG groups(all P<0.05). Both Yijing Decoction and minocycline effectively inhibited the elevated expression of CⅣ and LN induced by high glucose, and the difference between the YG, MG, and HG groups was statistically significant(all P<0.05). Futhermore, compared to the LG group, the protein expressions of MMP-2, MMP-3, and MMP-9 increased in the HG, MG, and YG groups(all P<0.05). Yijing Decoction specifically attenuated the high glucose-induced increase in MMP-2, MMP-3 and MMP-9 protein expression, and there were statistically significant differences between the YG and HG group(all P<0.05). No significant difference were observed in the expressions of TIMP-1 and TIMP-2 among the LG, HG, MG, and YG groups(all P>0.05).CONCLUSION:Yijing Decoction can potentially intervene in DR by modulating the protein expression of MMP-2, MMP-3, MMP-9, CⅣ, and LN, suppressing high glucose-induced BM remodeling, and mitigating damage to iBRB.