Background The pathogenesis of silicosis has not been fully elucidated, and microRNAs (miRNA) may be involved in the occurrence and development of silicosis. Objective To investigate the effect of miR-204-3p inhibitor on the epithelial-mesenchymal transition (EMT) process and silicosis fibrosis in silicon dioxide dust-induced alveolar epithelial cells. Methods A co-culture model of macrophages and epithelial cells was established using a Transwell chamber. NR8383 macrophages were seeded into the upper chamber of the Transwell, and RLE-6TN cells were seeded into the lower chamber. After 24 h of culture, the medium in the lower chamber was discarded, washed three times with phosphate-buffered saline (PBS), and replaced with serum-free medium. The cells were divided into four groups: control group, silicosis group, miRNA NC group, and miR-204-3p inhibitor group. The lower chamber was transfected with miRNA NC for the miRNA NC group or the miR-204-3p inhibitor for the miR-204-3p inhibitor group. The lower chambers of the remaining two groups were added by equal amounts of serum-free medium. After 24 h, except for the control group that received an equal volume of serum-free medium, the upper chambers of the remaining three groups were treated with 800 μg·mL⁻¹ silicon dioxide dust. Morphological changes in each group were observed under a microscope. The mRNA and protein expression levels of EMT-related factors, including α-smooth muscle actin (α-SMA), Vimentin, N-Cadherin, and E-Cadherin, were detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot. The mRNA and protein expression levels of fibrosis-related factors, including Collagen I, Collagen III, and Fibronectin, were also assessed by RT-qPCR and Western blot. The fluorescence expression intensities of α-SMA, N-Cadherin, and E-Cadherin were evaluated by immunofluorescence. Results The morphological observation revealed that RLE-6TN cells in the control group exhibited a regular oval shape. After treatment with silicon dioxide, the cells predominantly displayed a long spindle shape. Following the intervention with the miR-204-3p inhibitor, the number of long spindle-shaped cells increased, and the intercellular gaps widened. The RT-qPCR results showed that, compared with the control group, the silicosis group exhibited significantly higher relative mRNA expression levels of EMT-related markers (α-SMA, Vimentin, and N-Cadherin) (P<0.05), while the relative mRNA expression level of E-Cadherin was significantly reduced (P<0.05); the relative mRNA expression levels of fibrosis-related markers (Collagen I, Collagen III, and Fibronectin) were also significantly elevated (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group showed significantly increased relative mRNA expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), decreased E-Cadherin mPNA expression (P<0.05), and elevated mPNA expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The Western blot analysis indicated that, compared with the control group, the silicosis group had significantly higher protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), lower E-Cadherin protein expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited significantly elevated protein expression levels of α-SMA, Vimentin, and N-Cadherin (P<0.05), reduced E-Cadherin expression (P<0.05), and increased protein expression of Collagen I, Collagen III, and Fibronectin (P<0.05). The immunofluorescence analysis demonstrated that, compared with the control group, the silicosis group showed enhanced fluorescence intensities of α-SMA and N-Cadherin and reduced fluorescence intensity of E-Cadherin. Compared with the miRNA NC group, the miR-204-3p inhibitor group exhibited increased fluorescence intensities of α-SMA and N-Cadherin and decreased fluorescence intensity of E-Cadherin. Conclusion The miR-204-3p inhibitor may exacerbate the EMT process and silicosis fibrosis in silicon dioxide-induced RLE-6TN cells. miR-204-3p plays a negative regulatory role in silicosis fibrosis.

Objective:To explore the clinical characteristics and prognoses of severe autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).Methods:A retrospective analysis was performed. The clinical data of 12 patients with severe GFAP-A admitted to Department of Neurology, Guangdong 999 Brain Hospital from January 2018 to June 2023 were collected, including demography, clinical manifestations, MRI features, laboratory examination results (such as antibodies), treatments and prognoses.Results:Among the 12 patients, 9 were male and 3 were female, with an average onset age of (46.58±17.53) years. Primary symptoms included headache, limb weakness, limb numbness, mental disorder, epileptic seizure, and urinary and defecation disorder; 9 patients had fever before onset. With aggravated severe GFAP-A, 12 patients had impaired consciousness, 12 had respiratory failure, 6 had unstable blood pressure and heart rate, and 2 had status epilepticus. Cranial MRI indicated abnormal lesions in all 12 patients, including 10 with brainstem involvement (7 had involved medulla oblongata); 10 showed soft meningeal enhancement. In 8 patients received MRI of the whole spinal cord, 7 had abnormal spinal cord lesions; point-like enhancement of the whole spinal meninges was observed in 6 of the 7 patients. All 12 patients had positive cerebrospinal fluid GFAP-IgG, and 3 patients also had positive serum GFAP-IgG. All patients accepted glucocorticoids and immunoglobulin immunotherapy, and 1 patient was supplemented with mycophenolate mofetil; 8 patients had good prognosis, and 4 patients died. Pulmonary infection, hyponatremia, hypoproteinemia, and deep vein thrombosis were the common complications.Conclusion:Patients with severe GFAP-A mainly manifest as meningoencephalitis and meningoencephalomyelitis, and are likely involved medulla oblongata, enjoying rapid clinical progression; even with early immunotherapy, high mortality rate is still noted.

Objective To observe the value of 3D Res2Net deep learning model for predicting volume doubling time(VDT)of solid pulmonary nodule.Methods Chest CT data of 734 patients with solid pulmonary nodules were retrospectively analyzed.The patients were divided into progressive group(n=218)and non-progressive group(n=516)according to whether lung nodule volume increased by ≥25％during follow-up or not,also assigned into training set(n=515)and validation set(n=219)at a ratio of 7∶3.Then a clinical model was constructed based on clinical factors being significantly different between groups,CT features model was constructed based on features of nodules on 2D CT images using convolutional neural network,and 3D Res2Net model was constructed based on Res2Net network using 3D CT images as input.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was calculated.Taken actual VDT as gold standard,the efficacy of the above models for predicting solid pulmonary nodule'VDT≤400 days were evaluated.Results No significant difference of predicting efficacy for solid pulmonary nodule'VDT≤400 days was found among clinical model,CT feature model and 3D Res2Net model,the AUC of which was 0.689,0.698 and 0.734 in training set,0.692,0.714 and 0.721 in validation set,respectively.3D Res2Net model needed 5-7 s to predict VDT of solid pulmonary nodules,with an average time of(5.92±1.08)s.Conclusion 3D Res2Net model could be used to predict VDT of solid pulmonary nodules,which might obviously reduce manual interpreting time.

The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3'-terminal nucleotides via 2'-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2'-O-methylation at the RNA 3'-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3'-terminal 2'-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3'-terminal 2'-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3'-terminal 2'-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3'-terminal 2'-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.
Animals ; High-Throughput Nucleotide Sequencing ; Humans ; Methylation ; Mice ; MicroRNAs/genetics* ; Oxidative Stress ; RNA, Small Interfering/metabolism* ; Real-Time Polymerase Chain Reaction

Chemoradiotherapy ; Cohort Studies ; Epidemiology ; Gynecology ; Humans ; Joints ; Methods ; Neoplasm Metastasis ; Obstetrics ; Population Characteristics ; Propensity Score ; Proportional Hazards Models ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Survival Rate ; Uterine Cervical Neoplasms

Objective To establish a comprehensive method combining physical model experiment and numerical simulation for studying airflow state of upper respiratory tract. Methods Based on CT medical images published online, a three-dimensional (3D) model of human upper respiratory tract was reconstructed. Based on 3D printing technology, an experimental model of the upper respiratory tract was established and the flow process of respiration was measured. A numerical simulation model was created based on the meshing of upper respiratory tract model and the turbulent Realizable k-ε model. Results Firstly, the result of numerical simulation was compared with the experimental conditions, and good agreement was achieved. The numerical simulation results showed that the airflow in respiratory process was in a parabolic shape; the distribution of flow field, pressure on wall and vortex structure were different between inspiratory and expiratory phases; there were air residues in the upper and lower nasal passages during the respiratory exchange process. In addition, the effects of airflow on physiological environment of the upper respiratory tract were preliminarily analyzed through the steak line, pressure field and vortex structure distribution. Conclusions The method proposed in this paper has the characteristics of pertinence, rapidity and accuracy, which gives full play to the advantages of reliable physical experiments and fine numerical simulation, and is applicable for studying different problems of the upper respiratory tract in different cases, with a high value for personalized diagnosis and treatment in clinic.

Objective: The purpose of this study was to analyze the impact of surgery of primary sites on stage IVB cervical cancer patients from a population-based database, the Surveillance, Epidemiology and End Results (SEER). Methods: Propensity score matching was performed to minimize heterogeneity in patient between with-surgery group and without-surgery group. Clinicopathological characteristics were compared using the χ2 or Fisher's exact test. Survival analysis included the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Between 2010-2015, a total of 1,139 International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer patients receiving chemoradiotherapy (CRT) were included in this retrospective study. Within post-matching cohort, the median duration of overall survival (OS) in stage IVB cervical cancer patients receiving CRT was 22 months. The overall 5-year survival rate was 25.7%. The increasing American Joint Committee on Cancer T stage (T1 vs. T2, p=0.033, hazard ratio [HR]=1.79, 95% confidence interval [CI]=1.05–3.05; T1 vs. T3, p=0.003, HR=2.20, 95% CI=1.31–3.67; T1 vs. T4, p=0.037, HR=2.75, 95% CI=1.06–7.12) and visceral metastasis (with vs. without, p=0.038, HR=1.60, 95% CI=1.03–2.49) was reported as independent risk factors of OS. Surgery of primary sites combined with CRT tended to prolong the survival of stage IVB cervical cancer patients (p<0.001, HR=0.36, 95% CI=0.21–0.61) compared with CRT, especially for patients without visceral metastasis (p=0.005, HR=0.31, 95% CI=0.14–0.70). Conclusions In conclusion, patients with stage IVB cervical cancer may achieve their best outcomes through CRT combined with surgery of primary sites. However, it deserves large scale prospective clinical trials to confirm.

Objective: To investigate the effects of remifentanil combined with propofol on hemodynamics, inflammatory stress response and immune function in patients with acute abdomen complicated with septic shock. Methods: From June 2017 to August 2018, 112 patients with acute abdomen complicated with septic shock who admitted to the First Affiliated Hospital of Xiamen University were enrolled in the study.They were randomly divided into observation group and control group according to the digital table, with 56 cases in each group.The control group was anesthetized with sevoflurane combined with propofol.The observation group was anesthetized with remifentanil combined with propofol.The hemodynamic parameters of the patients entering the operating room(T0₎, 0.5h(T₁), 1h(T₂) and awake(T₃) after anesthesia were recorded.The intraoperative norepinephrine dosage was recorded.The inflammatory response, stress response and immune function indicators at T₀, T₂ and T₃ were recorded. Results: Compared with T₀, T₁ and T₂, the MAP of the two groups was higher at T₃, and the differences were statistically significant(t_{control group}=4.834, 4.484, 5.378, t_{observation group}=6.420, 7.006, 6.152, all P<0.05). Compared with T₀, the HR of the two groups was higher at T₃, and the differences were statistically significant(t_{control group}=5.943, t_{observation group}=7.722, all P<0.05). Compared with T₁ and T₂, CO of the two groups was higher at T₃, and the differences were statistically significant(t_{control group}=4.276, 2.262, t_{observation group}=6.318, 5.132, all P<0.05). There were no statistically significant differences in MAP, HR and CO between the two groups at T₀, T₁, T₂ and T₃(all P>0.05). The doses of norepinephrine in the observation group and the control group were (1 587.7±287.5)μg and (1 937.9±397.6)μg, respectively, and the difference was statistically significant(t=5.341, P<0.05). The serum levels of C reactive protein(CRP), tumor necrosis factor alpha(TNF-α) and interleukin 6(IL-6) increased with time in the two groups, and the differences were statistically significant(t_{control group}=17.06, 36.13, 19.07, 3.822, 9.466, 2.874, 14.18, 26.87, 16.21, t_{observation group}=11.72, 20.79, 11.01, 2.810, 6.559, 3.716, 10.52, 24.56, 17.64, all P<0.05). At T₂ and T₃, the serum levels of CRP, TNF-α and IL-6 in the observation group[T₂: CRP (89.63±17.65)mg/L, TNF-α (51.16±10.16)ng/L, IL-6 (34.26±6.25)ng/L, T₃: CRP (136.15±26.25)mg/L, TNF-α (58.64±11.12)ng/L, IL-6 (67.56±12.67)ng/L]were lower than those in the control group[T₂: CRP (112.15±22.34)mg/L, TNF-α (59.56±11.58)ng/L, IL-6 (42.65±8.37)ng/L, T₃: CRP (175.16±34.75)mg/L, TNF-α (65.79±11.35)ng/L, IL-6 (79.02±14.56)ng/L], the differences were statistically significant(t=5.919, 6.703, 4.080, 3.367, 6.010, 4.443, all P<0.05). Compared with T0, serum levels of epinephrine(E), cortisol(Cor) increased in two groups at T₂ and T₃, and the differences were statistically significant(t_{control group}=10.03, 8.096, 8.679, 7.029, t_{observation group}=6.473, 4.728, 6.330, 4.727, all P<0.05). Compared with T₂, serum levels of E and Cor in two groups at T₃ were decreased, and the differences were statistically significant(t_{control group}=2.400, 2.638, t_{observation group}=2.260, 2.162, all P<0.05). At T₂ and T₃, the serum levels of E, Cor in the observation group[T₂: E (286.36±41.02)ng/L, Cor (262.52±29.89)μg/L, T₃: E (270.35±33.59)ng/L, Cor (253.23±30.28)μg/L]were lower than those in the control group[T₂: E (312.56±38.75)ng/L, Cor (287.56±38.76)μg/L, T₃: E (295.79±35.12)ng/L, Cor (270.25±30.15)μg/L], the differences were statistically significant (t=3.457, 3.917, 3.828, 2.981, all P<0.05). At T₀, T₂ and T₃, there were no statistically significant differences in CD₃⁺, CD₄⁺, CD₈⁺ and CD₄⁺/CD₈⁺ between the two groups(all P>0.05). Conclusion Remifentanil combined with propofol anesthesia can make hemodynamics more stable in patients with acute abdomen complicated with septic shock, and can alleviate inflammation and stress response.

Objective To evaluate the effect of nimodipine combined with 7.5％ hypertonic saline (HS) on postoperative cognitive function in aged rats.Methods Ninety-six healthy male Wistar rats,aged 18 months,weighing 450-500 g,were assigned into 4 groups (n=24 each) using a random number table:splenectomy group (group S),nimodipine group (group N),group HS and nimodipine plus HS group (group N+HS).Nimodipine 1 mg/kg was intraperitoneally injected in group N.In group HS,7.5％ HS 4 ml/kg was injected via the caudal vein.The equal volume of normal saline was injected intraperitoneally or via the caudal vein in group S.Splenectomy was performed under sevoflurane anesthesia at 30 min after the end of administration.On 1 day before operation and 3 and 7 days after operation,Morris water maze test was performed,and blood sainples from the caudal vein were simultaneously collected for determination of the concentrations of serum S100β protein and neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay.Results Compared with group S,the frequency of crossing the original platform was significantly increased,the escape latency was shortened,and the concentrations of serum S100β protein and NSE were decreased at each time point after operation in N,HS and N+HS groups (P＜0.05).Compared with group N or group HS,the frequency of crossing the original platform was significantly increased,the escape latency was shortened,and the concentrations of serum S100β protein and NSE were decreased at each time point after operation in group N+HS (P＜0.05).Conclusion Nimodipine combined with 7.5％ HS exerts better efficacy than either alone in improving postoperative cognitive function in aged rats.

Human breast milk contains a good balance of nutrients.In recent years,researchers have found that it contains not only abundant nutrients,but also different active components,and MicroRNAs (miRNA) are included.MiRNA are endogenous non-coding RNA,consisting of 21 to 25 nucleotides in length.They play an important role in regulating a variety of biological processes.In the miRNA confirmed in human breast milk,let-7、miRNA-30b and miRNA-378 are highly expressed and researches have already demonstrated that these miRNA are participating in the regulation of adipocytes differentiation,lipid accumulation and sugar and lipid metabolism.