ObjectiveTo explore the effect of respiratory neuromuscular biphasic synchronous stimulation on weaning from ventilator dependence in patients with severe neurological disorders undergoing tracheotomy. MethodsFrom May, 2023 to March, 2025, 94 critically ill patients with nerve related tracheostomy and ventilator dependence admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University were randomly divided into control group (n = 47) and observation group (n = 47). The control group received conventional treatment and comprehensive rehabilitation, while the observation group received respiratory nerve and muscle biphasic synchronous stimulation therapy on this basis. The oxygenation index (PaO₂/FiO₂), diaphragm mobility, diaphragm thickening rate, maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), mechanical ventilation time and weaning success rate were compared before, and two and four weeks after treatment. ResultsThree cases in the control group and one in the observation group were dropped out. There was no significant difference in various indicators between two groups before treatment (P > 0.05). Two and four weeks after treatment, PaO₂/FiO₂, diaphragm movement, diaphragm thickening rate, MIP and MEP improved with the prolongation of time in both groups (F > 23.632,P < 0.001), and they were better in the observation group than in the control group (P < 0.05). The mechanical ventilation time was shorter (t = 2.287, P < 0.05) and the success rate of weaning was higher (χ² = 4.622, P < 0.05) in the observation group than in the control group. ConclusionThe respiratory neuromuscular biphasic synchronous stimulation can be applied to patients with severe neurological conditions who are dependent on tracheotomy ventilators, to accelerate the recovery of respiratory muscle strength, shorten the duration of mechanical ventilation, and increase the success rate of weaning from the ventilator.

Objective On the basis of the theory of the tumor metastatic state, this work aims to explore the metastasis trajectories and peripheral immune response patterns in patients with non-small cell lung cancer (NSCLC) receiving vital qi-strengthening and toxin-eliminating therapy (Fuzheng Juandu) and reveal the value of peripheral immunity in assessing vital qi deficiency during metastasis. Methods A retrospective study design was adopted. Patients with NSCLC admitted from January 1, 2018, to October 31, 2025 were enrolled. Data on metastasis status and peripheral immune indices were collected at the follow-up time points of one, two, three, and five years. Group-based trajectory modeling was used to fit metastasis trajectories, and the independent predictors of trajectory grouping were analyzed through multifactor and multiclassification logistic regression. Results A total of 184 patients with NSCLC were included, and three different groups of metastasis trajectories were identified, namely, the low-risk stable (46.74%, n=86), low-risk rising (13.59%, n=25), and high-risk stable (39.67%, n=73) groups. Univariate analysis revealed substantial differences in peripheral immune indices among the three trajectory groups. Multivariate analysis showed that TNM stage, absolute neutrophil count, lymphocyte count, absolute monocyte count, platelet volume, SAA:CRP ratio, and NLR were independent predictors of the low-risk rising group, whereas TNM stage, absolute monocyte count, basophil count, SII, and NLR were independent predictors of the high-risk stable group. Conclusion Under Fuzheng Juandu therapy, patients with NSCLC exhibit three distinct metastasis trajectories, each corresponding to a specific peripheral immune response pattern. Elucidating these peripheral immune response patterns may facilitate the objective quantification of the degree of vital qi deficiency, prediction of future metastasis risk, and providing an important reference for the individualized clinical implementation of Fuzheng Juandu therapy.

Piezo1 is a Ca²⁺-permeable mechanosensitive ion channel that plays a central role in mechanosensing and signal transduction in dental and periodontal tissues. In tooth tissue, Piezo1 is a key factor mediating dentin sensitive pain. The flow of dentinal tubule fluid induced by external stimulation can activate the Piezo1 channel on odontoblasts, triggering neuronal signals through the pannexin-1-purinergic 2X3 receptor (PANX-1-P2X3) receptor axis, resulting in pain perception. In addition, Piezo1 has a dual regulatory role in the process of pulp inflammation and repair : on the one hand, its expression is up-regulated in an inflammatory environment, which may aggravate pain sensitivity ; on the other hand, it activates the migration, proliferation and odontogenic differentiation of dental pulp stem cells by mediating Ca²⁺influx, ATP release and downstream purinergic 2X7 receptor (P2X7R), MEK / ERK signaling pathways, thereby promoting reparative dentin formation. In periodontal tissue, Piezo1 plays a central role in maintaining periodontal tissue homeostasis and regulating alveolar bone remodeling by sensing mechanical stimuli such as bite force. During orthodontic tooth movement, Piezo1 promotes osteogenic differentiation by activating Wnt / Ca²⁺, Notch and other pathways on the tension side. It affects osteoclast activity by regulating receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) balance on the pressure side. At the same time, Piezo1 is also a key regulator of periodontal immune microenvironment. It is expressed in immune cells such as macrophages, neutrophils and dendritic cells. Its activation can promote the polarization of macrophages to pro-inflammatory M1 type, enhance the release of pro-inflammatory factors and matrix metalloproteinases, and thus aggravate the inflammatory destruction of periodontal tissue.In view of its multiple functions, Piezo1 has become a potential therapeutic target, including local or systemic application of its inhibitors, mechanical intervention, physical therapy, gene therapy and stem cell therapy, showing a broad clinical transformation prospect in the treatment of oral diseases. In this paper, the structural characteristics, signal transduction mechanism of Piezo1 and its expression distribution, function and regulatory network in tooth tissue and periodontal tissue are reviewed, so as to provide ideas for the development of oral disease treatment strategies targeting Piezo1.

Objective To systematically review and quantify the content and structure of the non-accompanied wards policy texts at the provincial level in China from the perspective of policy tools,providing references and insights for optimizing and implementing future policies.Methods Using the policy analysis tools as framework,it applies content ana lysis to construct a two-dimensional analytical framework with the X-dimension and Y-dimension.A total of 19 policy texts related to non-accompanied ward issued by provincial governments in China from January 2000 to August 2024 were coded and analyzed.Results A total of 141 entries were coded.In the X-dimension,supply-oriented,demand-oriented,and environment-oriented policy tools accounted for 21.28%,19.86%,and 58.86%,respectively,indicating a greater reliance on environmental-oriented policy tools;In the Y-dimension,policies from the"12th Five-Year Plan"(16.31%),"13th Five-Year Plan"(14.89%),and"14th Five-Year Plan"(68.80%)phases were analyzed.The number of policies in the"14th Five-Year Plan"phase was the highest among the three periods.Conclusion The policy framework for non-accompanied wards in China is still in its initial exploration phase and has room for improvement.It is recommended that future policies optimize the use of policy tools,strengthen coordination among them,and support the development of non-accompanied wards.

Objective To evaluate the frailty status and risk factors among hospitalized elderly patients after percutaneous coronary intervention(PCI),and to provide a reference for improving and delaying their frailty.Methods From March to August 2024,using convenience sampling,patients aged over 75 years who underwent PCI in a tertiary cardiovascular disease specialist hospital in Beijing were selected as the survey participants.Patient-related informations were collected through a self-designed general information questionnaire.The Fried Phenotype Frailty Scale,the Katz Activities of Daily Living,Lawton Instrumental Activities of Daily Living(IADL)scale,the Charlson Comorbidity Index,the Morse Fall Scale,the Mini Nutritional Assessment-Short Form(MNA-SF),and the 15-item Geriatric Depression Scale(GDS-15)were evaluated postoperatively until discharge.Univariate and multivariate logistic analyses were conducted to identify factors associated with frailty among patients after PCI.Results A total of 278 patients were included.The incidence of frailty after PCI was 52.16％.Based on Fried Phenotype scores,patients were divided into a non-frail group and a frail group.Univariate analysis showed statistically significant differences between the 2 groups in terms of age,gender,hemoglobin,NT-ProBNP,LVEF,IADL scores,living alone status,nutrition status,falls risk,and depression level(P＜0.05).Multivariate logistic regression analysis revealed that age,Lawton IADL scores,falls risk,nutrition status,depression level were factors influencing frailty,with odds ratios of 1.167,0.575,1.597,0.399,and 3.610,respectively(P＜0.05).Conclusion The incidence of frailty is high among patients aged over 75 years after PCI,and there are multiple risk factors affecting their frailty status.Clinical healthcare providers should prioritize long-term management of these patients and implement comprehensive interventions with the consideration of their physiological,psychological,and social conditions.

Objective To investigate the therapeutic efficacy of combination of dapagliflozin and sacubitril valsartan on patients with heart failure(HF)complicated with type 2 diabetes mellitus(T2DM).Methods A retrospective study was conducted on 160 patients with HF and T2DM admitted to our hospital from November 2020 to November 2022.According to drug treatment,they were classified into sacubitril valsartan group(80 cases)and combined group(dapagliflozin combined with sacubitril valsartan,80 cases).After 3 months of treatment,the differences were compared between the two groups in following aspects:blood glucose fluctuations,left ventricular diastolic function,and vascular endothelial function,and the incidence of adverse events after 1 year of follow-up.Results After 3 months of treatment,serum FPG,2 h-PG and HbAlc levels,and MAGE,LAGE,MODD and SDBG values were significantly lower in the combined group than the sacubitril valsartan group(P＜0.05,P＜0.01).The combined group had obviously higher e'and LVEF values while lower LVMI and BNP levels than the other group(P＜0.05,P＜0.01).After 3 months of treatment,NO and FMD were notably higher[96.18±6.70 ng/L vs 92.34±6.85 ng/L,P=0.000;(8.25±1.16)％vs(7.72±1.28)％,P=0.007],while ET-1(59.72±4.95 ng/L vs 63.90±4.63 ng/L,P=0.000)was remarkably lower in the combined group than the sacubitril valsartan group.There was no statistical significance in the total incidence of adverse events between both groups after 1 year of follow-up(P＞0.05).Conclusion The combination of dapagliflozin and sacubitril valsartan has a significant improvement effect on blood glucose,left ventricular diastolic function and vascular endothelial function in T2DM patients with HF,with good drug safety.

Objective To investigate the factors influencing mood and sleep among special operation personnel,so as to provide evidence for the prevention and intervention of related issues.Methods A total of 600 special operation personnel during their special duty were enrolled by random sampling method.Basic information was collected by a general information questionnaire.Mood and sleep status were evaluated by self-rating anxiety scale(SAS),self-rating depression scale(SDS),and Pittsburgh sleep quality index scale(PSQI).Results Spearman correlation analysis showed that factors associated with anxiety were years of work experience(r=0.099,P=0.016),family residence(r=-0.153,P＜0.001),and sleep status(r=0.199,P＜0.001);the factors associated with depression were relationship with parents(r=-0.134,P=0.001),family residence(r=-0.144,P＜0.001),and sleep status(r=0.122,P=0.003);and the factors associated with sleep were age(r=0.088,P=0.031),years of work experience(r=0.079,P=0.049),and number of children(r=0.083,P=0.043).Binary logistic regression analysis showed that depression was not an influencing factor of sleep(odds ratio[OR]=1.302,95%confidence interval[95%CI]0.759-1.758,P=0.086),while anxiety was an influencing factor of sleep(OR=2.187,95%CI 1.608-4.695,P=0.001).Conclusion The sleep status of special operation personnel investigated in this survey is related to age and years of work experience,and is influenced by anxiety.Therefore,greater attention should be given to sleep issues in the occupational health support of special operations.Additionally,years of work experience,family residence,relationship with parents,and sleep status are related to anxiety and depression among special operation personnel.It is necessary to focus on the mental health of older workers and those with longer tenure.

Objective:To investigate the protective effects of p53/glucose transporter 4 (GLUT4) regulation on cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation.Methods:Human myocardial AC16 cells were treated with 33 mmol/L glucose and a hypoxic chamber to establish an in vitro model of high glucose combined with hypoxia/reoxygenation. Based on the glucose concentration in the medium and hypoxia/reoxygenation conditions, AC16 cells were divided into control group, high glucose group, hypoxia/reoxygenation group and high glucose combined with hypoxia/reoxygenation group. On the basis of high glucose combined with hypoxia/reoxygenation group, cells were transfected with empty vector, p53 small interfering RNA (siRNA), and co-transfected with p53 and GLUT4 siRNA to establish negative control group, sip53 transfection group, and sip53+siGLUT4 transfection group, respectively. Western blotting was used to detect the levels of hypoxia-inducible factor-1α (HIF-1α), p53, GLUT4, dynamin-related protein 1 (Drp1), mitofusin 2 (Mfn2), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine aspartic acid specific protease-3 (Caspase-3). The levels of reactive oxygen species were detected using the 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe. Mitochondria were labeled with the Mito-Tracker Deep Red FM fluorescent probe to assess mitochondrial morphology and their related parameters. Mitochondrial membrance potential was meausred using the JC-1 detection kit. Adenosine triphosphate (ATP) content was determined using an ATP assay kit. Glucose uptake ability was evaluated by measuring the fluorescence intensity of 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy- D-glucose (2-NBDG) using a multifunctional microplate reader. Apoptosis was assessed by TUNEL assay. Results:The relative expression of HIF-1α protein in the high glucose combined with hypoxia/reoxygenation group was 1.189±0.185, higher than that in the control group (0.086±0.071) ( P<0.05). The relative expression of p53 protein in the high glucose combined with hypoxia/reoxygenation group was 1.248±0.194, higher than those in the control group (0.730±0.184), high glucose group (0.932±0.161) and hypoxia/reoxygenation group (1.109±0.151) (all P<0.05). The relative expression of GLUT4 protein in the high glucose combined with hypoxia/reoxygenation group was 0.407±0.140, lower than those in the control group (1.061±0.060) and hypoxia/reoxygenation group (0.781±0.092) (both P<0.05). The fluorescence intensity of reactive oxygen species in the high glucose combined with hypoxia/reoxygenation group was 38.31±1.66, higher than that in the control group (11.59±1.02) ( P<0.05). The number of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (62.00±15.26), lower than those in the control group (136.20±23.55) and high glucose group (96.55±13.72) (both P<0.05). The average mitochondrial area in the high glucose combined with hypoxia/reoxygenation group was (7.02±1.38) μm 2, lower than those in the control group [(13.74±0.67) μm 2], high glucose group [(9.27±1.99) μm 2] and hypoxia/reoxygenation group [(9.64±2.36) μm 2] (all P<0.05). The average perimeter of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (9.10±1.14) μm, lower than those in the control group [(13.35±0.69) μm] and the hypoxia/reoxygenation group [(10.83±1.58) μm] (all P<0.05). The number of mitochondrial branches was 53.73±9.49, lower than those in the control group (147.10±25.99), high glucose group (97.08±13.65) and hypoxia/reoxygenation group (104.80±24.92) (all P<0.05). The average branch length of mitochondria in the high glucose combined with hypoxia/reoxygenation group was (1.45±0.26) μm, lower than that in the control group [(2.29±0.52) μm] ( P<0.05). The red-green fluorescence intensity ratio in the high glucose combined with hypoxia/reoxygenation group was 0.580±0.133, lower than those in the control group (2.379±0.242), high glucose group (1.200±0.112) and hypoxia/reoxygenation group (0.883±0.076) (all P<0.05). The ATP content of the high glucose combined with hypoxia/ reoxygenation group was (0.025±0.003) μmol/10 5 cells, lower than those of the control group [(0.137±0.012) μmol/10 5 cells], high glucose group [(0.078±0.003) μmol/10 5 cells] and hypoxia/reoxygenation group [(0.073±0.010) μmol/10 5 cells] (all P<0.05). The fluorescence intensity of 2-NBDG in the high glucose combined with hypoxia/reoxygenation group was 257 315±7 951, lower than those in the control group (339 597±10 165), high glucose group (317 293±8 876) and hypoxia/reoxygenation group (314 611±12 228) (all P<0.05). The relative expression of Drp1 protein in high glucose combined with hypoxia/reoxygenation group was 1.203±0.090, higher than those in the control group (0.705±0.170), high glucose group (0.910±0.106) and hypoxia/reoxygenation group (1.002±0.112) (all P<0.05). The relative expression of Mfn2 protein in the high glucose combined with hypoxia/reoxygenation group was 0.706±0.285, lower than those in the control group (1.988±0.139), high glucose group (1.305±0.076) and hypoxia/reoxygenation group (1.131±0.236) (all P<0.05). The relative expression levels of Bax/Bcl-2 and Caspase-3 proteins in the high glucose combined with hypoxia/reoxygenation group were 2.318±0.216 and 1.076±0.076, respectively, higher than those in the control group (0.281±0.046 and 0.442±0.084), high glucose group (0.673±0.043 and 0.662±0.159) and hypoxia/reoxygenation group (0.807±0.293 and 0.835±0.058), respectively (all P<0.05). The TUNEL fluorescence intensity of the high glucose combined with hypoxia/reoxygenation group was 70.55±7.22, higher than those of the control group (14.10±5.93), high glucose group (36.59±2.56) and hypoxia/reoxygenation group (39.04±6.016) (all P<0.05). The relative expression levels of p53 protein in the sip53 transfection group and sip53+siGLUT4 transfection group were 0.322±0.147 and 0.391±0.149, respectively, lower than that in the high glucose combined with negative control group (1.002±0.035) (both P<0.05). The relative expression of GLUT4 protein in the sip53 transfection group was 1.871±0.123, higher than that in the negative control group (1.281±0.232) ( P<0.05). The relative expression of GLUT4 protein in the sip53+siGLUT4 transfection group (0.951±0.193) was lower than that in the sip53 transfection group ( P<0.05). The fluorescence intensity of reactive oxygen species in the sip53 transfection group (27.73±0.74) was lower than that in the negative control group (38.83±0.83) ( P<0.05). The fluorescence intensity of reactive oxygen species in the sip53+siGLUT4 transfection group (43.12±5.08) was higher than that in the sip53 transfection group ( P<0.05). The number of mitochondria, the average area of mitochondria, the average perimeter of mitochondria, the number of mitochondrial branches and the average branch length of mitochondria in the sip53 transfection group were (92.27±10.10), (9.25±0.42) μm 2, (10.86±0.58) μm, (83.27±13.57), and (1.81±0.21) μm, respectively. They were higher than (52.36±16.87), (7.44±1.49) μm 2, (9.22±1.11) μm, (52.36±16.87), and (1.22±0.26) μm in the negative control group (all P<0.05). The number of mitochondria, the average area of mitochondria, the average perimeter of mitochondria, the number of mitochondrial branches and the average branch length of mitochondria in the sip53+siGLUT4 transfection group were (53.73±9.49), (6.89±0.61) μm 2, (8.88±0.47) μm, (53.73±9.49), and (1.22±0.17) μm, respectively, lower than those in the sip53 transfection group (all P<0.05). The red-green fluorescence intensity ratio, ATP content, 2-NBDG fluorescence intensity and relative expression of Mfn2 protein in the sip53 transfection group were 1.27±0.23, (0.048±0.021) μmol/10 5 cells, 275 923±10 447 and 2.608±0.581, respectively, higher than those in the negative control group [0.53±0.21, (0.020±0.007) μmol/10 5 cells, 254 875±8 078, and 0.687±0.146, respectively] (all P<0.05). The red-green fluorescence intensity ratio, ATP content, 2-NBDG fluorescence intensity and relative expression of Mfn2 protein in the sip53+siGLUT4 transfection group were 0.40±0.08, (0.011±0.012) μmol/10 5 cells, 199 511±6 855, and 0.649±0.070, respectively, lower than those in the sip53 transfection group (all P<0.05). The relative expression levels of Drp1, Bax/Bcl-2, Caspase-3 proteins and TUNEL fluorescence intensity in the sip53 transfection group were 0.759±0.063, 0.446±0.161, 1.048±0.300, and 48.93±1.48 respectively, lower than those (1.065±0.149, 1.197±0.133, 1.847±0.201, and 67.61±9.99) in the negative control group (all P<0.05). The relative expression levels of Drp1, Bax/Bcl-2, Caspase-3 proteins and TUNEL fluorescence intensity in the sip53+siGLUT4 transfection group were 0.958±0.166, 2.660±0.135, 1.587±0.220, and 63.39±12.84, respectively, higher than those in the sip53 transfection group (all P<0.05). Conclusions:Under the condition of high glucose combined with hypoxia/reoxygenation, p53 induces cardiomyocyte injury by down-regulating GLUT4. Inhibition of p53 can increase the expression of GLUT4, thereby reducing cardiomyocyte injury induced by high glucose combined with hypoxia/reoxygenation.

Objective:To explore the factors influencing adherence to voice therapy among patients with voice disorders in China. Methods:Patients with voice disorders who visited the Voice Therapy Center at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, from February to May 2022 were enrolled in the study. Adherence was assessed using the URICA-Voice scale, while influencing factors were assessed through the Voice Handicap Index（VHI） scale and a general information questionnaire. Correlation analysis was conducted using univariate and multivariate logistic regression analysis. Results:A total of 247 patients were included in the study, comprising 57 males（23.08%） and 190 females（76.92%）. The results revealed that: ①Female patients demonstrated higher likelihood of being in the contemplation stage（OR=0.22） compared to males. ②Patients with a monthly family income per capita>6 000 yuan were more likely to be in the contemplation stage than those with<3 000 yuan with an OR = 13.94. ③High vocal-demand occupations increased contemplation stage probability（OR=7.70） compared to moderate-demand occupations. ④Residence within 30-minute commute predicted action/maintenance stages（OR=7.14） versus≥60-minute commute. ⑤Patients whose occupations had high voice demands were more likely to be in the action and maintenance stages than those with average voice demands, with an OR of 16.20. Conclusion:Gender, monthly family income per capita, occupational voice demands, and distance to the hospital significantly impact the URICA-Voice compliance stages of patients. Patients who are female, have higher family income, have occupations with high voice demands, and live closer to the hospital exhibit higher compliance with voice training.
Humans ; Male ; Female ; Voice Disorders/therapy* ; Patient Compliance ; Voice Training ; Surveys and Questionnaires ; China ; Middle Aged ; Adult ; Voice Quality ; Logistic Models ; Aged

In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.