Obstructive sleep apnea (OSA) is a global public health concern characterized by repeated upper airway collapse during sleep. Research indicates that OSA is a risk factor for the development of various diseases, including cardiovascular disease, metabolic disorders, respiratory diseases, neurodegenerative diseases, and cancer. Exosomes, extracellular vesicles released by most cell types, play a key role in intercellular communication by transporting their contents-such as microRNA, messenger RNA, DNA, proteins, and lipids-to target cells. Intermittent hypoxia associated with OSA alters circulating exosomes and promotes a range of cellular structural and functional disturbances involved in the pathogenesis of OSA-related diseases. This review discusses the potential roles of exosomes and exosome-derived molecules in the onset and progression of OSA-associated diseases, explores the possible underlying mechanisms, and highlights novel strategies for developing exosome-based therapies for these conditions.
Humans ; Exosomes/physiology* ; Sleep Apnea, Obstructive/metabolism* ; Animals ; MicroRNAs/metabolism*

This study established a high performance liquid chromatography(HPLC) fingerprint of Chuanxiong Rhizoma from different producing areas and screened its potential differential components for producing areas by chemometrics. Furthermore, the content of the above differential components in Chuanxiong Rhizoma from different producing areas was measured and compared. Then, the geoherbalism markers(geo-markers) that can be used to distinguish Dao-di and non-Dao-di Chuanxiong Rhizoma were excavated by chemometrics. In fingerprint studies, a total of 27 common peaks were determined, and the fingerprint similarity for 37 batches of Chuanxiong Rhizoma samples from different producing areas was above 0.968. The orthogonal partial least squares-discriminant analysis(OPLS-DA) was capable of distinguishing Chuanxiong Rhizoma from Sichuan and from three other provinces, as well as Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. Meanwhile, 14 potential differential components in Chuanxiong Rhizoma from different provinces and 16 potential differential components in Chuanxiong Rhizoma from different producing areas in Sichuan were screened by the variable importance in projection(VIP) analysis under OPLS-DA. The reference standards were used to identify 10 potential differential components in the common peaks, and subsequent content determination verified that the content of the above 10 potential differential components was different among different producing areas. Then, the OPLS-DA and VIP analysis were performed with the content of the 10 potential differential components as variables. The results showed that Z-ligustilide, chlorogenic acid, and the ratio of butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Chuanxiong Rhizoma from Sichuan and Chuanxiong Rhizoma from Shaanxi, Hebei, and Jiangxi, while Z-ligustilide, n-butylphthalide, and the ratios of Z-ligustilide/senkyunolide A and butylidenephthalide/senkyunolide A were the geo-markers that can distinguish Dao-di Chuanxiong Rhizoma(from Dujiangyan) and non-Dao-di Chuanxiong Rhizoma(from other producing areas) in Sichuan province. This study elucidated the differences in material basis of Dao-di and non-Dao-di Chuanxiong Rhizoma based on fingerprinting and content determination combined with chemometrics, which provides a reference for the study of material basis of Dao-di traditional Chinese medicine.
Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Chemometrics/methods* ; Quality Control

OBJECTIVE: To compare the effectiveness of dynamic fixation and plate augmentation combined with bone grafting for femoral nonunion after interlocking intramedullary nails. METHODS: Between January 2008 and December 2022, a total of 128 patients who developed femoral nonunion following static fixation with interlocking intramedullary nailing were retrospectively analyzed. All patients underwent either dynamic intramedullary nail fixation or plate fixation with bone grafting while retaining the original intramedullary nail. There were 104 males and 24 females;the age ranged from 19 to 59 years old with an average of(32.70±9.21) years old. Patients were categorized into dynamization group and plate group based on the distinct treatment modalities. There were 67 patients in the dynamization group, comprising 54 males and 13 females. The age range was from 19 to 58 years old, with a mean age of (32.68±9.33) years old. All patients underwent open reduction and anterograde interlocking intramedullary nail fixation. Dynamic fixation was implemented between 10 and 28 months postoperatively.The plate group comprised 61 patients, of whom 50 were male and 11 were female. The age distribution ranged from 20 to 59 years old, with a mean age of (32.84±9.07) years old. All patients underwent open reduction and anterograde interlocking intramedullary nailing. Plate reinforcement fixation was performed between 10 and 30 months postoperatively. The incision length, duration of surgery, intraoperative blood loss, hospitalization period, fracture healing status, and incidence of complications were compared between the two groups of patients. RESULTS: All patients were followed up for a minimum duration of 1 year. The mean follow-up period for the dynamization group was(26.12±11.82) months, compared to (26.57±12.48) months for the plate group. No statistically significant difference was observed between the two groups (P>0.05). The incision size (2.73±1.21) cm, operation time (22.73±3.20) min and blood loss (19.06±6.22) ml in the dynamization group were significantly less than those in the plate group(22.53±2.24) cm, (126.40±13.91) min and(237.36±81.56) ml, respectively(P<0.05). All nonunion in the plate group were successfully healed, and the healing time duration ranged from 4 to 7 months with an average of(6.16±0.99) months. In the dynamization group, a total of 42 patients achieved fracture healing, with a healing duration ranging from 4 to 8 months with an average of (6.26±1.23) months. There was significant difference in healing rate between 2 groups (P<0.05), but there was no significant difference in healing time between 2 groups (P>0.05). The average treatment cost was(17 700.18±4 846.27) yuan in the plate group and (334.24±18.16) yuan in the dynamization group, and there was significant difference in costs between 2 groups (P<0.05). CONCLUSION Either dynamic fixation or plate augmentation combined with bone grafting is an effective method, but dynamic fixation is superior to plate augmentation combined with bone grafting for the treatment of femoral hyperplastic nonunion after interlocking intramedullary nails. Dynamic fixation offers several advantages, including simplified procedures, reduced trauma, and cost-effectiveness in medical expenses, making it superior to additional plate fixation combined with bone grafting. However, dynamic fixation is not suitable for the treatment of femoral atrophic nonunion.
Humans ; Male ; Female ; Adult ; Middle Aged ; Fracture Fixation, Intramedullary/adverse effects* ; Femoral Fractures/surgery* ; Fractures, Ununited/surgery* ; Bone Nails ; Retrospective Studies ; Bone Plates ; Young Adult

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

ObjectiveTo study the effect of Ziyin Mingmu Formula （滋阴明目方） on retinitis pigmentosa mice and its possible mechanism. MethodsSixty rd10 mice were randomly divided into model group， vitamin A group， and Ziyin Mingmu Formula low-， medium-， and high-dose groups， 12 mice in each group； twelve C57BL/6 mice as the blank group. The mice in Ziyin Mingmu Formula low-， medium-， and high-dose groups were given 13.5， 27.0 and 54.0 g/（kg·d） of Ziyin Mingmu Formula by gavage， respectively； mice in the Vitamin A group were given 750 IU/（kg·d） of vitamin A soft capsule by gavage； mice in the blank group and model group were given 13.5 ml/（kg·d） of physiological saline by gavage. Each group was gavaged once a day for 28 days. Fundus photography and optical coherence tomography were used to detect the morphology of the fundus and retina， TUNEL method was used to detect apoptosis， microtitre digital PCR and immunofluorescence double staining were used to detect glucose-regulated protein 78 （GRP78）， inositol-requiring enzyme 1 （IRE1）， activated transcription factor 6 （ATF6）， and C/EBP homologous protein （CHOP） mRNA and protein expression levels. ResultsIn the model group， optic discs were yellowish， fundus was atrophic with large pigmentation. The retinal blood vessels were thinned， a large number of vascular white sheaths were seen， the retinal cell nuclei disorganised， and a large number of apoptotic cells were seen； the fundus conditions of the mice in all dosages of Ziyin Mingmu Formula and the vitamin A group were improved to varying degrees compared with those of the model group， the apoptotic cells reduced， with Ziyin Mingmu Formula middle- and high-dose groups showing more significant improvement. Compared with the blank group， the retinal thickness of mice in the model group reduced， and the expression of GRP78， IRE1， ATF6， CHOP mRNA and protein elevated （P＜0.01）. Compared with the model group， retinal thickness increased and GRP78， IRE1， ATF6 mRNA and protein expression decreased in the vitamin A group and Ziyin Mingmu Formula medium- and high-dose groups； CHOP mRNA and protein expression decreased in low-， medium-， and high-dose groups of Ziyin Mingmu Formula （P＜0.05 or P＜0.01）. Compared with vitamin A group and the low-dose group of Ziyin Mingmu Formula， retinal thickness increased in the high-dose group of Ziyin Mingmu Formula （P＜0.01）. Compared with vitamin A group， GRP78， ATF6， IRE1， and CHOP mRNA expression decreased in the medium- and high-dose groups of Ziyin Mingmu Formula， and GRP78 and CHOP protein expression decreased （P＜0.05 or P＜0.01）. Compared with the low-dose group of Ziyin Mingmu Formula， CHOP protein expression reduced in the medium- and high-dose groups of Ziyin Mingmu Formula （P＜0.01）. ConclusionZiyin Mingmu Formula can reduce apoptosis of retinal tissues by inhibiting the endoplasmic reticulum stress response， thus slowing down the progression of retinopathy and protecting visual function in a dose-dependent manner.

Myocardial fibrosis （MF） is a common pathological manifestation of various heart diseases. Due to the non-renewable nature of myocardial cells， the occurrence of MF represents irreversible damage to the myocardium. Previous studies have suggested that fibroblast-mediated collagen deposition is the main mechanism of MF. Recent studies have found that there is an immune regulation mechanism in the heart itself， and macrophage activation/polarization plays an important role in MF. With the deepening of traditional Chinese medicine research， scholars have found that traditional Chinese medicine can interfere with MF by regulating the renin-angiotensin-aldosterone system （RAAS） system and the inflammatory process， repairing the extracellular matrix， managing oxidative stress， and maintaining the balance of autophagy. This process is closely related to the activation and M1/M2 polarization of macrophages. Throughout the MF process， macrophage activation is beneficial， but excessive activation will be harmful. In the early stage of MF， appropriate M1 macrophage polarization is conducive to activating immunity and removing harmful substances. In the middle and late stages of MF， appropriate M2 macrophage polarization is conducive to remodeling the damaged myocardium. If macrophage activation is excessive/insufficient， or the balance of M1/M2 macrophage polarization is broken， the effect changes from improvement to destruction. Traditional Chinese medicines that regulate the activation/polarization of macrophages have the effects of replenishing Qi and nourishing Yin， as well as regulating Qi and activating blood， but there are also some heat-clearing， dampness-drying， and detoxification products. Therefore， the occurrence of MF may be caused by Qi and Yin deficiency， damp heat accumulation， and Qi stagnation and blood stasis. By summarizing the biological processes involved in macrophage activation/polarization in MF， this paper expounded on the research progress of traditional Chinese medicine in regulating macrophage activation and M1/M2 polarization from different angles to improve MF， so as to provide a reference for the treatment of MF with traditional Chinese medicine.

Atrial functional mitral regurgitation (AFMR) is mitral regurgitation in patients with atrial fibrillation (AF), whose left atrium (LA) is enlarged, the left ventricle is not enlarged or only slightly enlarged, the left ventricular ejection fraction is preserved, and the mitral valve itself has no apparent lesion. At present, the etiology, pathophysiology and mechanism of this disease have not been completely clear yet. Existing studies have found that the causes of AFMR mainly include AF, enlargement of LA and mitral annulus, destruction of mitral annular shape, inability of mitral valve remodeling to compensate for mitral annular expansion, and hamstringing of the posterior mitral leaflet by atriogenic tethering. AFMR is demonstrated to be associated with an increased risk of mortality and readmission due to heart failure. Therefore, it serves as a primary therapeutic target for patients with heart failure and AF. However, the optimal treatment of AFMR still remains controversial. Therefore, this article will mainly expound the current definition, etiology, pathophysiological mechanism, treatment, and prognosis of AFMR.

Retinitis pigmentosa(RP)is a degenerative blinding disease characterized by the loss of the function of photoreceptor and retinal pigment epithelium. The activation of endoplasmic reticulum stress is a cellular defense regulatory mechanism, aimed at restoring the stability of endoplasmic reticulum function by self-regulation through a series of molecular signaling pathways. Rhodopsin mutation is a common cause of RP. Misfolding and retention of rhodopsin in endoplasmic reticulum and apoptosis of photoreceptor cells and retinal pigment epithelial cells induced by endoplasmic reticulum stress can lead to the occurrence and development of RP. This paper discusses endoplasmic reticulum stress and its role in the pathogenesis of RP and the role of endoplasmic reticulum stress inhibitors, traditional Chinese medicine and chemical drugs in regulating endoplasmic reticulum stress in RP treatment was summarized, in order to provide theoretical basis for endoplasmic reticulum stress in the clinical application of RP and provide new ideas for the research, prevention and treatment of RP.

Objective To investigate the diagnostic efficacy of the nomogram model based on Chinese thyroid ima-ging reporting and data system(C-TIRADS)combined with shear wave elastography(SWE)and clinically inde-pendent risk factors for category IV thyroid nodules.Methods 2D-ultrasound images and SWE images of 256 pa-tients(269 nodules)with category IV thyroid nodules were analyzed.The sensitivity,specificity,and accuracy of the diagnosis by C-TIRADS and SWE were calculated using pathological findings as the gold standard.Receiver op-erating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was obtained.Independent risk factors for thyroid nodules were screened by univariate and multifactorial logistic regression analyses,a risk model was developed and a nomogram model was plotted,and a calibration curve analysis was used to assess the accuracy of prediction.ROC of the nomogram model was plotted,and the diagnostic efficacy of C-TIRADS,SWE and nomogram model based on independent risk factors was compared according to the AUC in category IV thyroid nodules.Results The sensitivity,specificity,and accuracy of C-TIRADS for differentiating malignant and benign nodules was 0.921,0.724 and 0.844 respectively,the AUC was equal to 0.822 with a 95%confidence interval(95%CI)of 0.775-0.870.The sensitivity,specificity and accuracy of SWE were 0.701,0.981,0.814 respec-tively,and the AUC was 0.833(95%CI:0.795-0.872).Multifactorial logistic regression analysis suggested that C-TIRADS classification,mean value of elasticity(E-mean)age and aspect ratio were independent risk factors for identifying benign and malignant thyroid nodules.The sensitivity,specificity and accuracy of the nomogram model established based on the above four factors were 0.957,0.943 and 0.959,the AUC was 0.963(95%CI:0.943-0.984),which showed a diagnostic efficacy superior to that of C-TIRADS or SWE alone.Conclusion The nomogram model,constructed based on C-TIRADS,SWE and clinically independent risk factors,can improve the efficacy in diagnosing category IV thyroid nodules,with a better clinical application value.