[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

OBJECTIVE: To evaluate the safety and clinical therapeutic effect of in-line mechanical in-exsufflation to assist sputum clearance in patients with invasive mechanical ventilation. METHODS: A prospective observational study was conducted at the department of critical care medicine, the First Affiliated Hospital of Sun Yat-sen University from April 2022 to May 2023. Patients who were invasively ventilated and treated with in-line mechanical in-exsufflation to assist sputum clearance were enrolled. Baseline data were collected. Sputum viscosity, oxygenation index, parameters of ventilatory function and respiratory mechanics, clinical pulmonary infection score (CPIS) and vital signs before and after day 1, 2, 3, 5, 7 of use of the in-line mechanical in-exsufflation were assessed and recorded. Statistical analyses were performed by using generalized estimating equation (GEE). RESULTS: A total of 13 invasively ventilated patients using in-line mechanical in-exsufflation were included, all of whom were male and had respiratory failure, with the main cause being cervical spinal cord injury/high-level paraplegia (38.46%). Before the use of the in-line mechanical in-exsufflation, the proportion of patients with sputum viscosity of grade III was 38.46% (5/13) and decreased to 22.22% (2/9) 7 days after treatment with in-line mechanical in-exsufflation. With the prolonged use of the in-line mechanical in-exsufflation, the patients' CPIS scores tended to decrease significantly, with a mean decrease of 0.5 points per day (P < 0.01). Oxygenation improved significantly, with the oxygenation index (PaO₂/FiO₂) increasing by a mean of 23.3 mmHg (1 mmHg ≈ 0.133 kPa) per day and the arterial partial pressure of oxygen increasing by a mean of 12.6 mmHg per day (both P < 0.01). Compared to baseline, the respiratory mechanics of the patients improved significantly 7 days after in-line mechanical in-exsufflation use, with a significant increase in the compliance of respiratory system (Cst) [mL/cmH₂O (1 cmH₂O ≈ 0.098 kPa): 55.6 (50.0, 58.0) vs. 40.9 (37.5, 50.0), P < 0.01], and both the airway resistance and driving pressure (DP) were significantly decreased [airway resistance (cmH₂O×L^-1×s^-1): 9.6 (6.9, 10.5) vs. 12.0 (10.0, 13.0), DP (cmH₂O): 9.0 (9.0, 12.0) vs. 11.0 (10.0, 15.0), both P < 0.01]. At the same time, no new lung collapse was observed during the treatment period. No significant discomfort was reported by patients, and there were no substantial changes in heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure before and after the in-line mechanical in-exsufflation treatment. CONCLUSIONS The combined use of the in-line mechanical in-exsufflation to assist sputum clearance in patients on invasive mechanical ventilation can effectively improve sputum characteristics, oxygenation and respiratory mechanics. The in-line mechanical in-exsufflation was well tolerated by the patients, with no treatment-related adverse events, which demonstrated its effectiveness and safety.
Humans ; Prospective Studies ; Respiration, Artificial/methods* ; Respiratory Insufficiency/therapy* ; Sputum

BACKGROUND:Bone marrow mesenchymal stem cells have been widely used to treat neurological diseases.However,due to limitations of the blood-brain barrier,low survival rate and differentiation rate of stem cells at damaged sites,the therapeutic effect is limited. OBJECTIVE:To investigate the effects of Shexiang Huangqi compound dripping pills on proliferation,migration and astrocyte differentiation of bone marrow mesenchymal stem cells. METHODS:Male SD rats were treated with Shexiang Huangqi compound dripping pills for 5 days after continuous gavage.Blood was collected from the abdominal aorta and serum was separated for later use.The effect of 5%,10%and 20%drug-containing serum on the proliferation of bone marrow mesenchymal stem cells was detected by CCK-8 assay.The effect of 10%drug-containing serum on lateral migration of bone marrow mesenchymal stem cells was observed by scratch test.Bone marrow mesenchymal stem cells were cultured in Transwell cells.The effects of 10%drug-containing serum on longitudinal migration of bone marrow mesenchymal stem cells were observed by crystal violet staining and DAPI nuclear staining.Differentiation of bone marrow mesenchymal stem cells into astrocytes was observed by inducing solution with 10%drug-containing serum or co-culture with astrocytes. RESULTS AND CONCLUSION:(1)10%and 20%drug-containing serum promoted cell proliferation more significantly on days 2 and 3,and there was no statistical difference between the two concentrations.(2)At 30 and 48 hours,bone marrow mesenchymal stem cell migration in 10%drug-containing serum group was significantly higher than that in the control group.(3)The number of bone marrow mesenchymal stem cells filtered through Transwell cells in 10%drug-containing serum group was higher than that in the control group.(4)10%drug-containing serum might promote the differentiation of bone marrow mesenchymal stem cells to astrocytes,but the differentiation effect was weak,and astrocytes might further promote the differentiation of bone marrow mesenchymal stem cells into astrocytes induced by drug-containing serum.(5)The results exhibited that the 10%drug-containing serum could promote the proliferation and migration of bone marrow mesenchymal stem cells in vitro.Co-culture with astrocytes may promote the differentiation of bone marrow mesenchymal stem cells towards astrocytes.

Objective:To investigate the diagnostic value and imaging characteristics of MRI combined with 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/CT in focal cortical dysplasia (FCD) complicated with refractory epilepsy. Methods:A retrospective analysis was performed on 42 patients with FCD complicated with refractory epilepsy who were admitted to the Affiliated Hospital of Jining Medical University from January 2017 to December 2022. All patients underwent preoperative MRI and 18F-FDG PET/CT, and PET/MRI fusion was performed on the images. Chi-square test and Kappa consistency test were used to compare the localization diagnostic efficacy of PET/CT, MRI and PET/MRI fusion for epileptic foci. The patients were categorized based on gender, lesion location, pathological type, seizure type, and efficacy. Independent sample t-test and analysis of variance were used to compare maximum standardized uptake (SUVmax) values and asymmetry index (AI) of the patients between different groups. Results:Among the 42 patients, the positive rates of MRI, PET/CT, PET/MRI fusion examinations were 85.7%(36/42), 95.2%(40/42), 100.0%(42/42), the lateral localization rates were 71.4%(30/42), 92.9%(39/42), 95.2%(40/42), and the localization rates were 57.1%(24/42), 81.0%(34/42), 88.1%(37/42), respectively. There were significant differences in the lateral localization rates and localization rates of epileptogenic foci between MRI and PET/CT (χ 2=6.574, P=0.010; χ 2=5.570, P=0.018). There were significant differences in the positive rates of lesions, the lateral localization rates and the localization rates of epileptogenic foci between MRI and PET/MRI fusion (χ 2=6.385, P=0.012; χ 2=8.571, P=0.003; χ 2=10.118, P=0.001). There were no significant differences in the positive rates of lesions between MRI and PET/CT, and in the positive rates of lesions, the lateral localization rates and localization rates of epileptogenic foci between PET/CT and PET/MRI fusion (χ 2=2.184, P=0.139; χ 2=2.024, P=0.155; χ 2=0.210, P=0.647; χ 2=0.819, P=0.365). The Kappa consistency test of PET/CT and PET/MRI fusion imaging was performed for the location of epileptogenic foci, and the Kappa=0.721 was obtained, indicating that they were consistent in the location of epileptogenic foci. The SUVmax values of patients with temporal lobe epilepsy were lower, and the AI values were higher than that of patients with extra temporal lobe epilepsy (7.4±1.3 vs 9.6±1.6, 15.5±2.6 vs 12.9±2.4; t=5.154, 6.083; P=0.001, 0.001). The SUVmax values of patients with good efficacy (according to the Engel efficacy grading system, grades Ⅰ-Ⅱ indicating good efficacy) were higher, and the AI values were lower than that of patients with poor efficacy (according to the Engel efficacy grading system, grades Ⅲ-Ⅳ indicating poor efficacy; 9.5±1.9 vs 7.9±2.1, 13.5±3.3 vs 14.8±3.0; t=2.789, 3.722; P=0.042, 0.029). There were no significant differences in SUVmax and AI values among different genders, pathological types and seizure types (all P>0.05). Conclusions:The imaging characteristics of patients with different types of FCD complicated with refractory epilepsy are different. PET/MRI fusion is better than MRI in the diagnosis of FCD complicated with refractory epilepsy, and is consistent with PET/CT in the location of epileptogenic foci.

Objective: To investigate the changes in the levels of interleukin-6 (IL-6) and let-7e in rats induced by coal mine dust, so as to provide the basis for the mechanism of coal worker's pneumoconiosis (CWP). Methods: Sixty-four clean and healthy male Sprague-Dawley rats were randomly divided into the control group, coal dust group, mixed dust group (mixed coal and silica dust) and quartz group. The rats in the control group were exposed to 1 mL physiological saline by non-exposure tracheal perfusion, and the rats in the dust-exposed groups were exposed to 1 mL dust suspension. Rats were sacrificed by anesthesia after 1 month and 6 months, lung tissue was observed using hematoxylin-eosin staining, the pathological change in the lungs was scored using the Szapiel scoring system, the levels of IL-6 in the bronchoalveolar lavage fluid were detected using enzyme-linked immunosorbent assay, and the expression of let-7e was determined by quantitative real-time PCR. Results: A month after exposure, a small amount of coal spots and inflammatory exudation were observed in the lung tissue of the coal dust group and the mixed dust group. The quartz group showed tissue structure destruction and mild fibrosis and thickening of alveolar septum. Six months after exposure, there were more coal spots and slightly thickened alveolar septum in the coal dust group, and hyperplasia of pulmonary interstitial fibers, destruction of alveolar structure and silica nodules were observed in the mixed dust group. In the quartz group, the alveolar structure was obviously destroyed, the interstitial fiber proliferation was significant and silica nodules were seen. Two-factor analysis of variance showed that the interaction between duration of exposure and dust type significantly influenced the pathological score of lung tissue, IL-6 levels, and let-7e expression levels (P<0.05). Under the same dust type, the pathological score of lung tissue and IL-6 levels were higher at 6 months after exposure than at 1 month, while the relative expression of let-7e was lower at 6 months after exposure than at 1 month (all P<0.05). Under the same duration of exposure, the pathological score of lung tissue and IL-6 levels were higher in the dust-exposed groups than in the control group, while the relative expression of let-7e was lower in the dust-exposed groups than in the control group (all P<0.05). Conclusions Coal dust can cause an increase in levels of IL-6 and a decrease in let-7e expression in rats. The type of dust and duration of exposure can interactively affect IL-6 and let-7e.

Thyroid eye disease (TED) is an orbital disease closely associated with thyroid disorders, with 25%-50% of patients with diffuse toxic goiter (Graves Disease) developing secondary TED, which can lead to blindness and disability and significantly impair patients' visual function and quality of life.Activity staging is a crucial assessment index for TED and is essential for clinical evaluation, treatment planning, and prognosis.The Clinical Activity Score (CAS) is currently the most widely used method for this purpose both domestically and internationally.To improve the accuracy and consistency of CAS evaluations, the European Group of Graves' Orbitopathy (EUGOGO) recommended the use of a CAS scoring atlas in the TED guidelines.However, existing atlases are primarily based on Caucasians.Considering the anatomical differences in the orbit between Chinese and Caucasians and the resulting divergent ocular characteristics, there is a need for a comprehensive interpretation of the CAS scoring details in the current guidelines.This should be followed by further refinement to tailor the CAS scoring criteria to Chinese patients with TED.Such measures will standardize the operational methods and judgment criteria of CAS scoring in China, thereby providing a reliable basis for the accurate diagnosis and treatment of the disease.

Abstract: This study reviews the prevalence, pathogens, transmission routes, and impacts on human health of natural focal diseases in Xizang Autonomous Region, with the goal of offering scientific evidence for the prevention and control of these diseases in the region. By collecting relevant literature and data, the prevalence of natural focal diseases in Xizang Autonomous Region, including echinococcosis, plague, giardiasis, and brucellosis, were summarized. Additionally, the distribution of pathogens, primary transmission routes, and prevention and control strategies for these diseases were analyzed. The results revealed that the focal diseases in Xizang Autonomous Region exhibit diversity and complex epidemiological patterns, with zoonoses being widely prevalent in agricultural and pastoral areas. Therefore, to effectively prevent and control focal diseases in Xizang Autonomous Region, it is essential to strengthen the monitoring and control of pathogens, improve environmental and personal hygiene, and enhance public health awareness and preventive knowledge among residents. Moreover, it is necessary to establish a robust early warning system and preventive control strategies. Effective integrated measures will contribute to reducing disease incidence and ensuring the health of the local population as well as the sustainable development of agriculture and animal husbandry.

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.
Animals ; Humans ; Sarcopenia/metabolism* ; Forkhead Box Protein O3/metabolism* ; Muscle, Skeletal/metabolism* ; Aging/metabolism* ; Primates/metabolism*

Objective:To investigate the effect of long non-coding RNA00461 (LINC00461) on apoptosis of triple negative breast cancer cells.Methods:RT-qPCR was used to detect the expression of LINC00461 in normal breast epithelial cells MCF-10A, TNBC cell lines MDA-MB-231 and MDA-MB-468. The apoptosis rate was detected by Annexin V-FITC/PI double staining cell apoptosis kit. Western blot was used to detect apoptosis-associated protein. The localization of LINC00461 in cells was detected by FISH. RNA pulldown and RIP were used to detect the interaction between LINC00461 and c-Myc. The effect of LINC00461 on TNBC apoptosis was verified by subcutaneous tumorigenesis in nude mice.Results:Compared with MCF-10A, LINC00461 expression in MDA-MB-231 and MDA-MB-468 cells was significantly increased. Interference with LINC00461 significantly reduced the expression of LINC00461 and c-Myc protein. Overexpression of LINC00461 significantly decreased the expression level of apoptosis-related protein. Overexpression of LINC00461 significantly reduced the apoptosis rate by 50%-70%, with a statistically significant difference. FISH results showed that LINC00461 was mainly localized in the cytoplasm. RNA pulldown results showed that LINC00461 interacted with c-Myc. RIP results showed that the concentration of LINC00461 in c-Myc group was more than 400%, and the difference was statistically significant. In addition, overexpression of c-Myc reduced the promotion effect of knockdown LINC00461 on the apoptosis rate of 30%-50%. In animal experiments, overexpression of LINC00461 significantly increased tumor volume (50%-80%) and tumor weight (30%-50%) .Conclusion:LINC00461, mainly located in the cytoplasm, regulates the apoptosis of TNBC cells, and its molecular mechanism may be that LINC00461 interacts with c-Myc protein to play an important role in regulating the apoptosis of TNBC cells.

Objective:To explore the protective effect of methyl eugenol (Me) on islet ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism.Methods:The islets were isolated and purified from 6-8 week male BALB/c mice and divided into four groups of normal control (normal culture without any treatment), hypoxia/reoxygenation (H/R treatment), H/R+ dimethyl sulfoxide (DMSO dosing plus H/R treatment) and H/R+ Me (Me dosing plus H/R). Viability of islet cells in each group was detected by acridine orange (AO)/propidium iodide (PI) double stain.Function of islet cells (insulin secretion) was measured by enzyme-linked immunosorbent assay (ELISA). Murine islet β Min6 cells were selected for detecting the effect of Me on the proliferative activity of normal cultured and H/R treated islet cells under different concentration gradients by CCK8.Then Min6 cells were divided into four groups of normal, H/R, H/R+ DMSO and H/R+ Me.The definition of group was the same as that of primary murine islets.Flow cytometry and Hoechst 33342 nuclear stain were utilized for detecting cell apoptotic rate in each group.The protein expressions of p-JNK, p-p38, JNK, p38, Bcl-2 and Bax were detected by Western blot.And the data were processed by one-way ANOVA or t test.Results:The proportion of dead islet cells in H/R group was (29.47±2.65)% and it was significantly lower than that in normal group (7.63±1.53)%.And the inter-group differences were statistically significant ( P<0.001). The proportion of dead islet cells was (20.63±3.07)% in H/R+ Me group.It was higher than that in H/R group (29.47±2.65)% and in H/R+ DMSO group (30.13±1.50)% and inter-group difference was statistically significant ( P<0.05 & P<0.01). Under the stimulation of high glucose, the insulin secretion level of islet in H/R+ Me group was (1.76+ 0.08) mg/L, which was higher than that in H/R group and H/R+ DMSD group(1.24±0.14)mg/L and(1.27±0.05)mg/L, and the difference was statistically significant[(1.76±0.08) vs. (1.24±0.14) mg/L; (1.76±0.08) vs.(1.27±0.05) mg/L, P<0.01]. There was no significant effect on cell viability after Me dosing within a certain concentration range (0-40 μmol/L). After Me dosing (5 μmol/L), cell viability of H/R-treated Min6 cells was significantly higher than that without Me.And the difference was statistically significant[(1.19±0.03) vs.(1.00±0), P<0.01]. As compared with H/R and H/R+ DMSO groups, overall apoptotic rate declined in H/R+ Me group (Hoechst 33342 stain: 14.50%±1.05% vs. 23.30%±1.18%, 14.50%±1.05% vs. 22.77%±1.75%, P<0.001; Flow cytometry: 4.36%±0.54% vs. 21.44%±1.02%, 4.36%±0.54% vs. 21.68%±3.06%, P<0.01). The expressions of p-JNK and p-p38 were down-regulated (p-JNK: 0.77±0.06 vs. 1.03±0.05, 0.77±0.06 vs.0.93±0.04, P<0.001; p-p38: 0.80±0.05 vs. 1.01±0.08; 0.80±0.05 vs. 1.00±0.05, P<0.05) while Bcl-2/Bax ratio rose (1.62±0.13 vs. 0.72±0.10, 1.62±0.13 vs. 0.74±0.13, P<0.01). Conclusions:Me can improve the viability and function of islets and suppress the apoptosis of Min6 cells after H/R.The mechanism is correlated with JNK and p38 MAPK signaling pathways.