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.

ObjectiveTo evaluate the impact of stroke on diaphragmatic function by ultrasound. MethodsFrom April, 2024 to June, 2025, 40 stroke patients (stroke group) were recruited in Xuanwu Hospital Capital Medical University. Additionally, 40 sex- and age-matched healthy subjects (control group) were recruited without directional selection. Diaphragmatic excursion and diaphragmatic thickness during quiet breathing and deep breathing were assessed using ultrasound in both groups, and the diaphragmatic thickening fraction was calculated. The stroke group was further divided into two subgroups according to disease course: ≤ 30 days group and > 30 days group, for subgroup analysis. ResultsDuring both quiet and deep breathing, diaphragmatic excursion on the affected side in the stroke group was smaller than that on the unaffected side and in the control group (P < 0.05). During quiet breathing, diaphragmatic thickening fraction on the affected side in the stroke group was smaller than that on the unaffected side and in the control group (P < 0.05), while the diaphragmatic thickening fraction on the unaffected side was significantly smaller than that in the control group (P < 0.01). During deep breathing, the bilateral diaphragmatic thickening fraction in the stroke group was significantly smaller than that in the control group (P < 0.001), and the bilateral end-inspiratory diaphragmatic thickness was significantly smaller than that in the control group (P < 0.001). During quiet breathing, diaphragmatic excursion in both the ≤ 30 d group and the > 30 d group was smaller than that in the control group (P < 0.05); during deep breathing, diaphragmatic excursion in the ≤ 30 d group was smaller than that in the control group (P < 0.05). In both quiet breathing and deep breathing, the diaphragmatic thickening fraction in the ≤ 30 d group and the >30 d group were lower than those in the control group (P < 0.05). During deep breathing, end-inspiratory diaphragmatic thickness in both the ≤ 30 d group and the > 30 d group was significantly smaller than that in the control group (P < 0.01). ConclusionUltrasound can effectively identify the impact of stroke on patients' diaphragmatic function. In stroke patients, both diaphragmatic excursion and contractile performance are reduced on the affected side, while contractile performance is also reduced on the unaffected side.

OBJECTIVES: Exposure to rare earth elements (REEs) has been linked to various systemic diseases, but their impact on the offspring blood-brain barrier (BBB) via the gut-brain axis remains unclear. This study aims to investigate the effects of maternal exposure to neodymium oxide (Nd₂O₃) on the BBB integrity of offspring rats, and to evaluate the potential protective role of bifidobacterium tetrad viable tablets (BTVT) against Nd₂O₃-induced intestinal and BBB damage. METHODS: Healthy adult SD rats were mated at a 1:1 male-to-female ratio, with the day of vaginal plug detection marked as gestational day 0. A total of 60 pregnant rats were randomly assigned to the following groups: Control, 50 mg/(kg·d) Nd₂O₃, 100 mg/(kg·d) Nd₂O₃, 200 mg/(kg·d) Nd₂O₃, and 200 mg/(kg·d) Nd₂O₃ + BTVT group. Treatments were administered by daily oral gavage throughout pregnancy and lactation. On postnatal day 21 (weaning), offspring feces, brain, and colon tissues were collected. Hematoxylin and eosin (HE) staining was used to assess structural changes in brain and intestinal tissues. Short-chain fatty acids (SCFAs) in feces were quantified by gas chromatography-mass spectrometry (GC-MS). Evans Blue (EB) dye extravasation assessed BBB permeability. Gene and protein expression levels of tight junction proteins occludin and zonula occludens-1 (ZO-1) were measured by reverse transcription PCR (RT-PCR) and Western blotting (WB), respectively. Neodymium levels in brain tissue were determined via inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: HE staining revealed that maternal Nd₂O₃ exposure caused mucosal edema, increased submucosal spacing, and lymphocyte infiltration in offspring colon, as well as neuronal degeneration and vacuolization in brain tissue. BTVT intervention alleviated these changes. GC-MS analysis showed that levels of acetic acid, propionic acid, butyric acid, and isobutyric acid significantly decreased, while valeric acid and isovaleric acid increased in offspring of Nd₂O₃-exposed mothers (P<0.05). BTVT significantly restored levels of acetic, propionic, and isobutyric acids and reduced valeric acid content (P<0.05). EB permeability was significantly elevated in Nd₂O₃-exposed offspring brains (P<0.05), but reduced with BTVT treatment (P<0.05). RT-PCR and WB showed downregulation of occludin and ZO-1 expression following Nd₂O₃ exposure (P<0.05), which was reversed by BTVT (P<0.05). ICP-MS results indicated significantly increased brain neodymium levels in offspring from all Nd₂O₃-exposed groups (P<0.05), while BTVT significantly reduced neodymium accumulation compared to the 200 mg/(kg·d) Nd₂O₃ group (P<0.05). CONCLUSIONS Maternal exposure to Nd₂O₃ during pregnancy and lactation disrupts intestinal health and BBB integrity in offspring, elevates brain neodymium accumulation, and induces neuronal degeneration. BTVT effectively mitigates Nd₂O₃-induced intestinal and BBB damage in offspring, potentially through modulation of the gut-brain axis.
Animals ; Female ; Blood-Brain Barrier/pathology* ; Pregnancy ; Rats, Sprague-Dawley ; Rats ; Male ; Neodymium/toxicity* ; Prenatal Exposure Delayed Effects/prevention & control* ; Lactation ; Maternal Exposure/adverse effects* ; Brain

Objective:To investigate the application value of intraoperative electrocochleography（ECochG） monitoring technique and insertion techniques in cochlear implant（CI） and analyze its relationship with postoperative residual hearing（RH） preservation. Methods:Thirty-one patients（35 ears） who received CI in our hospital from June 2022 to July 2024 were enrolled. The Advanced Bionics Active Insertion Monitoring（AIM） system was used for real-time ECochG monitoring during surgery. Intraoperative cochlear microphonics （CM） waveform changes were recorded and analyzed in relation to postoperative RH preservation. Results:①ECochG recordings were successfully obtained in 34 of 35 ears （97.1%）. ②According to Harris classification, there were 7 ears（20.6%） of Type A（rising）, 7 ears（20.6%） of Type C（declining）, 8 ears（23.5%） of Type CC（fluctuating）, and 12 ears（35.3%） of Type D（no response）. ③The total CM amplitude decrease was significantly moderately correlated with postoperative low-mid frequency hearing loss（r=0.67, P=0.017）. The total CM amplitude decrease was significantly moderately correlated with postoperative low frequency hearing loss（r=0.65, P=0.023）. ④For the mean amplitude variation, the Amax was 30.70 μV, the Amin was 8.64 μV, and the Aend was 18.27 μV. ⑤Sixteen cases completed postoperative follow-up, with an average low-mid frequency（125-1 000 Hz） residual hearing loss of 15.25 dB HL and a RH preservation rate of 87.5%. Conclusion:Intraoperative ECochG monitoring can effectively predict postoperative residual hearing changes, effectively guide surgical manipulation, and improve residual hearing preservation rate.
Humans ; Cochlear Implantation/methods* ; Audiometry, Evoked Response ; Cochlear Implants ; Male ; Female ; Adult ; Middle Aged ; Monitoring, Intraoperative ; Adolescent ; Young Adult ; Minimally Invasive Surgical Procedures ; Child ; Aged ; Postoperative Period