Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

ObjectiveTo investigate the mechanisms of Runmu Dihuang decoction （RMDHD） in treating perimenopausal dry eye with liver-kidney Yin deficiency syndrome based on the silent information regulator 3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty female Sprague-Dawley rats were randomly divided into six groups （n=10 per group）： Sham operation group， model group， sodium hyaluronate eye drop group， and low-， medium-， and high-dose RMDHD groups （5.625， 11.25， 22.50 g·kg^-1）. Except for the sham operation group， all rats underwent bilateral ovariectomy and were administered 0.1% benzalkonium chloride eye drops combined with long-term chronic irritation to establish a perimenopausal dry eye model with liver-kidney Yin deficiency syndrome. Drug administration began in the 11th week after modeling and continued for 21 days. General conditions， screen-grip test scores， tear secretion volume， tear film breakup time （TFBUT）， and corneal fluorescein staining were recorded. Serum levels of reactive oxygen species （ROS）， follicle-stimulating hormone （FSH）， estradiol （E₂）， and progesterone （PROG） were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the lacrimal glands， corneas， and uteri were observed using hematoxylin-eosin （HE） staining. Protein expression levels of SIRT3， HIF-1α， phosphorylated NF-κB p65 （p-NF-κB p65）， and total NF-κB p65 in the lacrimal glands were detected by Western blot. The expression of inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the lacrimal glands was assessed by immunohistochemistry （IHC）. ResultsAfter model establishment， no significant differences were observed among the groups except the sham operation group. Compared with the sham operation group， the other groups exhibited slowed movement， dull responses， increased irritability， reduced body weight， elevated rectal temperature， decreased screen-grip test scores， reduced tear secretion， and significantly shortened TFBUT （P<0.05）. After treatment， compared with the model group， the sodium hyaluronate eye drop group and all RMDHD groups showed improved general conditions， significantly increased tear secretion （P<0.05）， prolonged TFBUT （P<0.05）， and elevated screen-grip test scores （P<0.05）. Serum ROS and FSH levels were significantly decreased， while E₂ and PROG levels were significantly increased （P<0.05）. Pathological damage to the cornea， lacrimal glands， and uterus was ameliorated. In addition， protein expression levels of SIRT3 and HIF-1α in the lacrimal glands were significantly upregulated （P<0.05）， whereas the expression of p-NF-κB p65， IL-1β， and TNF-α was significantly downregulated （P<0.05）. ConclusionRMDHD increases tear secretion and TFBUT， improves lacrimal gland and corneal injury， and alleviates dry eye symptoms in a perimenopausal dry eye rat model with liver-kidney Yin deficiency syndrome. The underlying mechanism may be related to regulation of the SIRT3/HIF-1α/NF-κB signaling pathway， inhibition of oxidative stress and inflammatory responses， and reduction of ocular surface tissue damage.

Objective To investigate the clinical features of patients with neuromyelitis optica spectrum disorders （NMOSD） mainly manifesting as somnolence， and to improve the awareness of this disease among clinicians. Methods A retrospective analysis was performed for the medical records of nine patients with NMOSD who were admitted to Xuanwu Hospital， Capital Medical University， from May 2021 to May 2024 and had the main clinical manifestation of somnolence， including general information， cranial and/or spinal MRI findings， polysomnography （PSG） results， cerebrospinal fluid （CSF） routine parameters， aquaporin-4 （AQP4） antibody， the level of orexin in CSF， treatment response， and prognosis. Results The age of onset in the nine patients ranged from 18 to 62 years， with a median of 30 （24，47） years， and the male/female ratio was 1∶8. Among the nine patients， six had the initial symptom of somnolence， three developed somnolence after other symptoms， and five had the manifestations of other diencephalic syndromes. All nine patients were tested for AQP4 in CSF and serum and were found positive for AQP4 antibody in CSF and/or serum. All nine patients had abnormal signals in both thalami and para-third ventricles on cranial MRI. Three patients underwent PSG and were found to have a shortened sleep latency and sleep architecture disorder， among whom one had the electrophysiological manifestation of narcolepsy and one had the manifestation of hypoventilation in severe sleep apnea. The level of orexin in CSF was measured for two patients， and the results showed that the level of orexin was lower than the normal level in both patients. All nine patients received glucocorticoid pulse therapy， and some patients were given intravenous immunoglobulin and/or subsequent sequential immunotherapy. All patients had a significant improvement in the symptom of somnolence at discharge. Conclusion In the core symptoms of NMOSD， acute diencephalic syndrome manifesting as somnolence is relatively rare in clinical practice and is easily misdiagnosed in the early stage， and the possibility of NMOSD should be considered for unexplained somnolence. Imaging examination and AQP4 antibody detection are of significant value for the diagnosis of this disease， and sleep monitoring can provide an objective assessment of sleep status. Immunotherapy is the main treatment method for this disease， and most patients have a good prognosis.

Objective To explore the relationship between intestinal flora imbalance and pulmonary function in patients with chronic obstructive pulmonary disease (COPD), and to analyze the related influencing factors. Methods A total of 310 patients with COPD who were admitted to Air Force Military Medical University Tangdu Hospital from June 2022 to December 2024 were retrospectively analyzed. Based on intestinal flora status, the enrolled patients were classified into imbalance group (n=83) and non-imbalance group (n=227). Logistic regression analysis was conducted to analyze the independent related factors of intestinal flora imbalance in COPD patients. Based on the above factors, a prediction model was constructed, and ROC curve analysis model was applied to analyze the predictive value of the model on intestinal flora imbalance. Results Logistic regression analysis revealed that age, IL-6, albumin, pulmonary function, long-term bed rest and long-term use of antibiotics were related to intestinal flora imbalance in COPD patients (all P<0.05). ROC results of the Logistic prediction model showed that the area under the curve, sensitivity, specificity and 95%CI were 0.961, 0.880, 0.996 and 0.932-0.989 respectively. Conclusion The intestinal flora imbalance in patients with COPD is closely related to lung function, age, inflammatory status, nutritional indicators, activity ability and antibiotic use.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo develop and validate a nomogram based on the albumin-bilirubin （ALBI） score for predicting the risk of severe perioperative complications in patients undergoing hepatectomy for hepatolithiasis. MethodsA retrospective analysis was conducted on the clinical data of 163 hepatolithiasis patients who underwent hepatectomy. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for severe perioperative complications. A nomogram prediction model was constructed and its performance was evaluated. ResultsAmong the 163 patients， 66 and 97 were classified into the low-grade and high-grade ALBI groups， respectively. Significant intergroup differences were observed in gender， total bilirubin， albumin levels， and the incidence of severe complications （P0.05）. Severe complications occurred in 40 patients. Independent risk factors included age 60 years （OR=5.49， P0.001）， high-grade ALBI （OR=8.30， P0.001）， history of biliary surgery （OR=2.60， P=0.035）， hepatectomy （segmentectomy）≥3 （OR=2.75， P=0.028）， and open surgical approach （OR=4.00， P=0.009）. A nomogram for predicting severe perioperative complications was successfully established. Internal validation showed that the model had an area under the ROC curve （AUC） of 0.865， which outperformed traditional single predictors. The calibration curve closely aligned with the ideal curve， with a mean absolute error （MAE） of 0.027. Decision curve analysis （DCA） demonstrated a net clinical benefit when the threshold probability exceeded 10%， superior to that of traditional predictors. ConclusionThe ALBI score-based nomogram is successfully developed and validated to predict the risk of severe perioperative complications in hepatolithiasis patients undergoing hepatectomy. The model demonstrated favorable predictive performance and high clinical utility， serving as an effective tool for both preoperative risk assessment and postoperative risk stratification.

Objective To study a method for determining the cumulative dose of low-energy neutrons ( < 100 keV) independently based on a CR-39 detector. Methods According to the theory of track etching kinetics, the differences in the tracks formed by low-energy neutrons or fast neutrons in a BN + CR-39 detector under broad-spectrum neutron irradiation were analyzed. A method was proposed to identify the tracks produced by low-energy neutrons under specific etching conditions while avoiding interference from fast neutron tracks. Results Experimental results demonstrated that the BN + CR-39 detector using TASTRAK PADC CR-39 track-detecting plastic could independently detect the tracks of low-energy neutrons when etched in a 6.25 mol/L NaOH solution for 1 h. The track density showed a good linear relationship with the ambient dose equivalent of low-energy neutrons, and the calibration coefficient was 0.0366 μSv·tr⁻¹·cm². Conclusion The BN + CR-39 detector proposed in this study demonstrated high sensitivity to low-energy neutrons. The track identification method can be used for effective and independent determination of the cumulative dose equivalent of low-energy neutrons.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.

ObjectiveBased on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， the effects of Huanglian Zhimutang on glucose and lipid metabolism disorders and hepatic insulin resistance （IR） with type 2 diabetes mellitus （T2DM） were investigated. MethodsGoto-Kakizaki （GK） rats were fed a high-fat diet to induce a T2DM rat model and then randomly divided into four groups： normal control group， model control group， metformin group （0.10 g·kg^-1）， and Huanglian Zhimutang group （3.60 g·kg^-1）， with eight rats in each group. Drug intervention was administered continuously for 8 weeks. Serum and liver tissues were collected from each group. Fasting insulin （FINS） levels were measured using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. Total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured using an automatic biochemical analyzer. Liver tissue pathology was observed via hematoxylin-eosin （HE） staining. Serum interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） levels were detected using ELISA. Network pharmacology and transcriptomics sequencing were combined to analyze differentially expressed genes （DEGs） in liver tissue from the normal control group， model control group， and Huanglian Zhimutang group. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify pathways affected by Huanglian Zhimutang intervention in T2DM. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of insulin receptor substrate-1 （IRS-1）， PI3K， Akt， and peroxisome proliferator-activated receptor gamma （PPARγ） in liver tissue， while Western blot was used to evaluate corresponding protein expression levels. ResultsAfter 8 weeks of Huanglian Zhimutang intervention， typical symptoms of T2DM rats such as polydipsia， polyphagia， and polyuria were significantly alleviated， along with reductions in fasting blood glucose levels and insulin resistance（P<0.01）. Histopathological results revealed that Huanglian Zhimutang effectively improved hepatic steatosis and inflammatory edema and reduced lipid vacuole formation. Biochemical tests demonstrated that Huanglian Zhimutang significantly reduced serum levels of TC， TG， and LDL-C（P<0.01）. ELISA results showed that Huanglian Zhimutang effectively decreased serum concentrations of IL-6 and TNF-α（P<0.05，P<0.01）. Combined network pharmacology predictions with KEGG pathway analysis of transcriptomics showed that DEGs between the Huanglian Zhimutang and model control groups were significantly enriched in the PI3K/Akt signaling pathway. Real-time PCR and Western blot results confirmed that Huanglian Zhimutang upregulated the expression of PI3K/Akt signaling pathway-related mRNAs and proteins in liver tissue（P<0.05，P<0.01）， thereby reducing inflammation， alleviating hepatic lipid accumulation， and enhancing insulin sensitivity. ConclusionHuanglian Zhimutang effectively ameliorates glucose and lipid metabolism disorders in T2DM rats. Its mechanism may be related to the regulation of the PI3K/Akt pathway， which reduces inflammation and hepatic lipid deposition and relieves hepatic insulin resistance.