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

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Retinal vein occlusion(RVO)is the second most common blinding retinal vascular disease, and its secondary macular edema(ME)is an important cause of visual function impairment in patients. Intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs serves as the first-line treatment, yet it is confronted with such issues as the need for repeated injections and non-response in some patients. Imaging and laboratory biomarkers play a crucial role in the early accurate diagnosis, prediction of disease progression, and evaluation of visual prognosis of RVO-ME. This study systematically reviews the research progress of imaging and laboratory biomarkers related to the prognosis of RVO-ME after anti-VEGF treatment in recent years, covering imaging biomarkers like central retinal thickness and ellipsoid zone integrity, as well as laboratory biomarkers such as serum APLN and aqueous humor IL-6. It summarizes the associations between different biomarkers and the prognosis of anti-VEGF therapy, aiming to provide a basis for the early accurate assessment and optimization of individualized treatment for RVO-ME patients, which holds significant clinical reference value.

OBJECTIVES: To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). METHODS: Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. RESULTS: We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. CONCLUSIONS TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals ; Gastrointestinal Microbiome/drug effects* ; Signal Transduction/drug effects* ; Mice ; ErbB Receptors/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Diarrhea/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Anti-Bacterial Agents/adverse effects* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation

Objective To investigate the effect of community management model on elderly patients with non-valvular atrial fibrillation(NVAF),and to provide methods and ideas for the management of elderly patients with NVAF in community.Methods A prospective randomized controlled trial was conducted in 305 elderly patients with NVAF who visited two community health service centers in Hefei and Wuhu from De-cember 2022 to November 2023.The patients were randomly divided into the control group(n=152)and the experimental group(n=153)by random number table method.The control group received routine diagnosis and treatment measures,while the experimental group adopted the community management model.Both groups were treated for 6 months.The New York Heart Association(NYHA)cardiac function classification was used to evaluate patients'cardiac function,the European Heart Rhythm Association(EHRA)score was used to assess patients,atrial fibrillation symptoms,the Morisky Medication Adherence Scale(MMAS-8)was used to evaluate patients'medication adherence,and the general self-efficacy scale(GSES)was used to assess patients'self-efficacy.The ventricular rate,control of cardiovascular risk factors,use rate of anticoagulant drugs,and the incidence of bleeding and arterial embolism were recorded in both groups.Results After 6 months of intervention,the NYHA cardiac function classification,EHRA score and ventricular rate control in the experimental group were better than those in the control group,and the patients'MMAS-8 and GSES scores were higher.The compliance rate of blood pressure and fasting blood glucose,and the use rate of antico-agulant drugs in the experimental group were higher than those in the control group.There was no statistical-ly significant difference in the incidence of bleeding and arterial embolism between the two groups(P>0.05).Conclusion The community management model can improve the symptoms,cardiac function,use rate of anticoagulant drugs,and medication adherence of elderly NVAF patients,and enhance their quality of life.

Objective To investigate the expression of myelin transcription factor 1-like(MYT1L)during amyotrophic lateral sclerosis(ALS)progression and its association with neuronal degeneration through bioinformatics analysis combined with in vivo and in vitro experiments.Methods Bioinformatics analysis of the GSE106803 dataset from the Gene Expression Omnibus(GEO)database revealed significant down-regulation of MYT1L in spinal cords of ALS transgenic mice carrying the human superoxide dismutase 1 mutant gene(hSOD1G93A)compared to the wild-type(WT)mice.hSOD1G93A transgenic mice and their WT littermates were selected to analyze MYT1L mRNA and protein changes in spinal cord tissues at different disease stages using Real-time PCR and Western blotting.Double immunofluorescent staining was used to determine the distribution and cellular localization of MYT1L in the spinal cord of mice at the middle stage of the disease.An ALS cellular model was established using hSOD1G93A mutant NSC34 cells,with hSOD1WT NSC34 cells as controls.MYT1L expression and distribution were assessed in these cells via Real-time PCR,Western blotting,and immunofluorescent staining.Based on the GSE76220 dataset from the GEO database,differentially expressed genes(DEGs)between MYT1L high-and low-expression groups in lumbar spinal motor neurons of ALS patients were identified,followed by Gene Ontology(GO)functional enrichment analysis.MYT1L overexpression was induced in the ALS cellular model to evaluate alterations in cell viability and neurite outgrowth.Results In the GSE106803 dataset,MYT1L expression was significantly down-regulated in the spinal cord of ALS mice.Animal experiments confirmed progressive reductions in MYT1L mRNA and protein levels in spinal cord tissues of ALS mice during mid-and late-disease stages.Compared to the WT group,MYT1L expression decreased in motor neurons of the lumbar spinal cord gray matter anterior horn in ALS mice,while it increased in astrocytes.In vitro,hSOD1G93Amutant NSC34 cells exhibited significantly reduced MYT1L expression than controls,with MYT1L localized to both the cytoplasm and nucleus.DEGs between MYT1L high-and low-expression groups in lumbar spinal cord motor neurons of ALS patients(GSE76220 dataset)were enriched in synaptic-related functions through GO analysis.Overexpression of MYT1L in hSOD1G93A mutant NSC34 cells enhanced cell viability and promoted neurite outgrowth.Conclusion Aberrantly low expression of MYT1L is closely associated with ALS pathogenesis.Overexpression of MYT1L promotes neurite growth and exerts protective effects on ALS motor neurons,suggesting its therapeutic potential.

Objective:To explore the prognostic value of systemic immune-inflammatory index(SII)combined with tumor burden score (TBS) (hereinafter referred to as STS) in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection, and to construct a nomogram model.Methods:The clinical data (including the degree of tumor differentiation, vascular cancer thrombus, and lymph node metastasis, etc.) of 258 ICC patients who received radical resection at People′s Hospital of Zhengzhou University (170 cases, training set) and Cancer Hospital of Zhengzhou University (88 cases, validation set) from January 1, 2016 to January 31, 2020 were retrospectively analyzed and graded by SII, TBS and STS. Multivariate Cox regression analysis were used to identify independent factors affecting the prognosis of patients with ICC. Kaplan-Meier survival curve and receiver operating characteristic curve (ROC) were drawn to evaluate the predictive efficiency of SII, TBS and STS in the overall survival of patients with ICC after radical resection. The nomogram prediction model was constructed and evaluate the performance of nomogram model using consistency index (C-index) and calibration curve.Results:Among 170 ICC patients in the training set, there were 106 cases of SII grade 1 and 64 cases of SII grade 2; 137 cases of TBS grade 1 and 33 cases of TBS grade 2; and 98 cases of STS grade 1, 47 cases of STS grade 2, and 25 cases of STS grade 3. Among 88 ICC patients in the validation set, there were 33 cases of SII grade 1 and 55 cases of SII grade 2; 66 cases of TBS grade 1 and 22 cases of TBS grade 2; and 30 case of STS grade 1, 39 cases of TBS grade 2, and 19 cases of TBS grade 3.The multivariate Cox regression analysis showed that tumor differentiation degree (highly differentiated vs. moderately differentiated HR=0.157, 95% confidence interval(95% CI) 0.045 to 0.546, highly differentiated vs. poorly differentiated HR=0.452, 95% CI 0.273 to 0.750), STS (grade 3 vs. grade 2 HR=1.966, 95% CI 1.148 to 3.469; grade 3 vs. grade 1 HR=1.405, 95% CI 0.890 to 2.216), vascular cancer thrombus ( HR=2.006, 95% CI 1.313 to 3.066), nerve invasion ( HR=1.865, 95% CI 1.221 to 2.850), and lymph node metastasis ( HR=1.802, 95% CI 1.121 to 2.896) were independent influencing factors of overall survival in ICC patients after radical resection (all P<0.05). The Kaplan-Meier survival curve showed that SII, TBS, and STS were independent influencing factors of overall survival in ICC patients (all P<0.05). The results of ROC analysis showed that the areas under the curve of SII, TBS and STS in predicting overall survival of ICC patients after radical resection were 0.566 (95% CI 0.479 to 0.652), 0.585 (95% CI 0.499 to 0.672), and 0.657 (95% CI 0.522 to 0.692), respectively. Tumor differentiation, vascular tumor thrombus, nerve invassion, lymph node metastasis, and STS were included to constract the nomogram model. The C-indexes of the training set and validation set based on the nomogram model were 0.792 (95% CI 0.699 to 0.825) and 0.776 (95% CI 0.716 to 0.833), respectively. The calibration curves of the survival rate of the training set and the validation set were close to the reference lines, and the nomogram model had better predictive ability in both the training set and the validation set. Conclusions:Preoperative STS grading is an effective and practical predictor of overall survival in ICC patients after radical section. Compared with SII and TBS alone, it has better predictive value for the prognosis of patients with ICC.

Objective: Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. Methods: We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3–12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). Results: The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004–1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. Conclusion Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.

Objective: The anterior controllable antedisplacement and fusion (ACAF) technique is a new procedure for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) that requires management of the disc adjacent to the ossification. This study describes a novel technique to reduce the number of fixed segments, namely, the “Klotski technique.” The efficacy of ACAF using the Klotski technique was compared with that of anterior cervical corpectomy and fusion (ACCF) in the treatment of OPLL with en bloc type dural ossification (DO). Methods: The clinical data of 25 patients with severe OPLL and en bloc type DO who were treated by the ACAF Klotski technique or ACCF at our hospital from January 2020 to January 2022 were retrospectively analyzed. In the Klotski technique, the number of segments fused within the OPLL is limited. The antedisplacement space was designed according to the shape of the vertebrae-OPLL-DO complex (VODC). Then, the entire VODC was antedisplaced as in Klotski. Neurological function and image examination were assessed preoperatively and postoperatively. Complications associated with surgery were recorded. Results: Patients were followed up for 24–36 months. There were 11 patients who were treated with ACAF and 14 patients who were treated with ACCF. At 2 weeks after surgery, the incidence of neurological deterioration was 21.4% (3 of 14) in the ACCF group and 9.1%(1 of 11) in the ACAF group. The incidence of intraoperative cerebrospinal fluid leakage (CFL) was 35.7% (5 of 14) in the ACCF group and 9.1% (1 of 11) in the ACAF group. The postoperative follow-up JOA scores of the patients in both groups were significantly better than their preoperative JOA scores (p<0.05). Conclusion The Klotski technique for ACAF is a good option for the treatment of patients with en bloc type OPLL-DO, as it limits the number of fused segments, has a low incidence of CFL and neurologic deficits and is associated with good neurological recovery.

Deep sternal wound infection (DSWI) is one of the potential and catastrophic complications after cardiac surgery. Despite the use of smaller incisions, routine application of prophylactic antibiotic and optimized blood glucose management, the incidence rate of DSWI still fluctuates between 1% and 5%. The early symptoms and signs of DSWI are not often obvious, making it too late for the clinicians to intervene in the process. Once left untreated, DSWI carries a very high mortality rate. Therefore, early prevention, diagnosis, and appropriate management of DSWI are crucial in preventing its progression to life-threatening outcomes. Considering the clinical severity and treatment complexity of DSWI, this article focuses on preventive experiences in each stage of DSWI, and reconstructive strategies after DSWI happens, raising attention among the medical community regarding DSWI.