Objective To introduce the research progress in the immune of composite tissue allotransplantation. Methods The related articles were reviewed to summarize the immune characteristics, experimental developments, and cl inical experiences of composite tissue allotransplantation. Results Composite allogeneic tissue is on the body surface, including the composition of the complex with high antigenicity. There are a lot of differences in the immune responsesbetween composite tissue allotransplantation and organ transplantation, such as immunosuppressant protocol, rejectiondiagnosis, and chronic rejection. Conclusion In the next study, it is urgently needed to learn these experiences and toestabl ish the special standard of composite tissue allotransplantation in induction of immune tolerance, local medication, and rejection diagnosis.
ObjectiveTo investigate the effect and mechanism of microRNA (miR)-146a-3p on acute lung injury (ALI) and inflammation induced by lipopolysaccharide (LPS) in mice.MethodsThirty-two BALB/c mice were randomly divided into sham group, ALI group, ALI+agomiR-negative control (NC) group, ALI+miR-146a-3p agonist (agomiR-146a-3p) group, with 8 mice in each group. The ALI model was established by instilling 5 mg/kg LPS into the lungs through the trachea, and the same amount of saline was instilled slowly in the sham group. The mice in the ALI+agomiR-146a-3p group/NC group were injected with 8 mg/kg agomiR-146a-3p or agomiR-NC respectively through the tail vein, once a day, for 3 days. The sham group and the model group were given the same amount of normal saline injection through the tail vein. After 24 hours, they were sacrificed and lung tissues were collected. The expressions of miR-146a-3p and toll-like receptor 4 (TLR4) mRNA in lung tissue were detected by RT-qPCR, the expression levels of TLR4, cleaved caspase-3, Bcl-2 related X protein (Bax), B cell lymphoma-2 (Bcl-2) protein in lung tissue were detected by Western blot. The changes of lung pathology were observed by hematoxylin-eosin staining. The apoptosis of lung tissue was detected by TdT-mediated dUTP nick-end labeling. The expression levels of IL-1β, IL-6 and TNF-α in lung tissue were detected by enzyme-linked immunosorbent assay (ELISA). The dual luciferase reporting system verified the targeting relationship between miR-146a-3p and TLR4 in MRC-5 cells. MRC-5 cells were divided into control group, LPS group, LPS+miR-146a-3p mimic group, LPS+pcDNA3.1(pc)-TLR4 group, LPS+miR-146a-3p mimic+pc-TLR4 group. 100 nmol/L miR-146a-3p mimic and pc-TLR4 plasmids were transfected into MRC-5 cells separately or jointly for 24 hours, and then treated with 1000 ng/mL LPS or normal saline for 72 hours. The apoptosis rate was detected by flow cytometry. The expression levels of TLR4, cleaved caspase-3, Bax, and Bcl-2 proteins were detected by Western blot. The levels of IL-1β, IL-6 and TNF-α were detected by ELISA.ResultsCompared with the ALI group, the expression of miR-146a-3p was up-regulated, the expressions of TLR4 mRNA and protein were down-regulated, the apoptotic rate was decreased, the expressions of cleaved caspase-3 and Bax protein was down-regulated, the expression of Bcl-2 protein was up-regulated, and the levels of TNF-α, IL-6 and IL-1β in lung tissue were decreased in the lung tissues of the ALI+agomiR-146a-3p group (P<0.05). Dual-luciferase reporter assay confirmed that miR-146a-3p regulates transcription by targeting TLR4 3’UTR sequence (P<0.05). Compared with the LPS group, the expression of TLR4 protein in MRC-5 cells of the LPS+miR-146a-3p mimic group was down-regulated, the apoptosis was reduced, the expressions of cleaved caspase-3 and Bax protein were down-regulated, and the levels of TNF-α, IL-6 and IL-1β in lung tissue were decreased (P<0.05). Overexpression of TLR4 reversed the effect of miR-146a-3p mimic overexpression on LPS-induced apoptosis and inflammation of MRC-5 cells (P<0.05).ConclusionmiR-146a-3p alleviates LPS-induced ALI in mice by down-regulating TLR4.
Objective To compare the differences of flow and volume responses in patients with mild to very severe chronic obstructive pulmonary disease（COPD） in bronchodilatation test. Methods The different changes of FEV1 and FVC in 217 patients with mild to very severe COPD（GOLD stage Ⅱ-Ⅳ） after inhaling salbutamol were analyzed retrospectively. Results FEV1 and FVC of the patients with COPD at stage Ⅱ-Ⅳ increased remarkably after inhaling β2 agonist，while there were significant differences between the changes of FEV1 and FVC. Increment of FEV1 and FVC (ΔFEV1 and ΔFVC)，representing flow and volume responses respectively，showed a normal distribution. The majority of patients fell in the range of ΔFEV1 from 0.00 to 0.04，0.05 to 0.09 and 0.10 to 0.14 liter，and ΔFVC from 0.00 to 0.09，0.10 to 0.19 and 0.20 to 0.29 liter. There was significant difference of ΔFEV1 among stage Ⅱ-Ⅳ patients with COPD （Plt;0.01），namely more severe the disease less ΔFEV1 got.In the other hand ΔFVC increased along with the progression of COPD，although no significant difference of ΔFVC among stage Ⅱ-Ⅳ patients with COPD was found. Though different changes of ΔFEV1 and ΔFVC were revealed，there was a positive correlation between ΔFEV1 and ΔFVC in patients at each GOLD stage and the correlation became more insignificant with the progression of COPD. Conclusions There are significant differences between post-bronchodilator flow and volume responses in patients with COPD.Flow response decreases remarkably along with the progression of COPD，whereas volume response increases along with the progression of COPD.
Abstract： As the most common blunt thoracic injury, lung contusion may develop into acute lung injury, adult respiratory distress syndrome or ventilation associated pneumonia, which can cause a high mortality. However, the pathogenesis and pathophysiology of lung contusion is not well understood yet. Stress is laid by many researchers on inflammatory response in the pathogenesis of lung contusion. We review the potential role of inflammatory response in the pathogenesis and pathophysiological changes of lung contusion. Emphasis is put on studies of inflammatory cells, mediators, receptors, surfactant dysfunction, and the potential role of epithelial cell or neutrophil apoptosis. The animal models are essential to the study of lung contusion and the studies examining secondary injuries exacerbating lung contusion are also noted.
ObjectiveTo summarize the mechanism of neutrophil extracellular traps (NETs) in hepatic ischemia-reperfusion injury (HIRI) and the research progress in targeting NETs to reduce HIRI, providing valuable reference for reducing HIRI. MethodThe related literatures at home and abroad about the role of NETs in the pathogenesis of HIRI and target NETs to alleviate HIRI were retrieved and reviewed. ResultsHIRI usually appeared in the process of liver surgery and was a common clinical problem, which occured in situations such as liver surgery, organ transplantation, liver ischemia and so on. This kind of injury would lead to tissue necrosis, inflammatory response and oxidative stress, which was a major cause of hepatic dysfunction and multiple organ failure after hepatic surgery, greatly increases the complications and mortality after hepatic surgery. NETs played a crucial role in the aseptic inflammatory response induced by hepatic ischemia/reperfusion. During hepatic ischemia-reperfusion, neutrophils promoted inflammatory cascade reactions and cytokine storms by forming NETs, exacerbating damage caused by hepatic ischemia-reperfusion. At present, some experimental and clinical studies had shown that inhibiting the formation of NETs or eliminating the formed NETs could alleviate the hepatic ischemia-reperfusion injury and improve the prognosis. ConclusionsTargeting NETs may become a new method for treating hepatic ischemia-reperfusion injury. In the future, it is foreseeable that more experiments and clinical trials will be conducted on targeted NETs for the treatment of hepatic ischemia-reperfusion injury. And gradually establish more comprehensive and effective treatment strategies, thereby providing new ways to improve the prognosis of hepatic surgery patients in clinical practice.
ObjectiveTo summarize the therapeutic targets of pancreatic cancer (PC).
MethodsThe related literatures about the therapeutic targets of PC were reviewed.
ResultsPC was one of the most challenging tumor in worldwide, and was characterized as a highly aggressive disease with poor overall prognosis and a high mortality rate. The hallmark of PC was its poor response to radio-and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches which could significantly improve the clinical outcome of PC had been described, involving signal-transduction pathways, immune response, stroma reaction, and epigenetic changes.
ConclusionsMany therapeutic targets are involved in the treatment of PC. As current therapies failed to significantly improve the progression and the survival of PC, new therapeutic approaches and clinical studies are strongly required.
ObjectiveTo investigate the influence of endoplasmic reticulum stress (ERS) on smoking-induced nucleus pulposus cells apoptosis and inflammatory response.MethodsBetween October 2016 and October 2018, 25 patients with cervical disc herniation receiving discectomy were collected and divided into smoking group (14 cases) and non-smoking group (11 cases). The baseline data of age, gender, herniated segment, and Pfirrmann grading showed no significant difference between the two groups (P>0.05). The obtained nucelus pulposus tissues were harvested to observe the cell apoptosis via detecting the apoptosis-related proteins (Caspase-3 and PRAP) by TUNEL staining and Western blot test. The nucleus pulposus cells were isolated and cultured with enzyme digestion, of which the third generation cells were used in follow-up experiments. Then, the expressions of inflammatory factors [interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α)] were detected by ELISA; the nuclear translocation of P65 was monitored by cell immunofluorescence staining. Furthermore, ERS-related proteins (GRP78 and CHOP) were detected by Western blot; and endoplasmic reticulum ultrastructure was observed under transmission electron microscope. To verify the regulatory effect of ERS, cells were pretreated by ERS specific inhibitor (4-PBA), then cell apoptosis and inflammatory response were tested.ResultsThe nucleus pulposus tissue observation showed that the cell apoptotic rate and the expressions of apoptosis-related proteins (Caspase-3 and PARP) were obviously higher in smoking group than in non-smoking group (P<0.05). The nucleus pulposus cells observation indicated that the expressions of the inflammatory factors (IL-1β and TNF-α) and the ERS-related proteins (GRP78 and CHOP) were also higher in smoking group than in non-smoking group (P<0.05). The results of cell immunofluorescence staining further confirmed that smoking stimulated nuclear translocation of P65 in nucleus pulposus cells. The ERS injury was much more serious in smoking group than in non-smoking group. Furthermore, after 4-PBA inhibiting ERS, the expressions of GRP78, CHOP, IL-1β, TNF-α, and P65 were significantly decreased (P<0.05), and flow cytometry results showed that cell apoptotic rate in smoking group was decreased, showing significant difference compared with the non-smoking group (P<0.05).ConclusionSomking can stimulate cell apoptosis and inflammatory response in nucleus pulposus cells via ESR pathway. Suppressing ESR may be a novel target to suspend smoking-induced intervertebral disc degeneration.
Objective To evaluate the changes in depressive symptoms and emotional responses in obstructive sleep apnea (OSA) patients after six months of continuous positive airway pressure (CPAP) therapy. Methods From June 2021 to December 2023, adult patients diagnosed with OSA at our hospital who were recommended for CPAP therapy as a first-line treatment were recruited. Demographic data (age, body mass index, gender), oxygen desaturation index, maximum duration of apnea and maximum duration of apnea were recorded. The patients were divided into a CPAP group and a non-CPAP group according to whether they were compliant to CPAP treatment. All patients completed questionnaires (including CES-D, DERS, ERS, and ESS) at 0, 1, 2, 4, and 6 months. Differences in general data and questionnaire results were compared between the two groups. Results The patients in the CPAP group showed significantly lower levels of depression and daytime sleepiness at 1, 2, 4, and 6 months compared with the non-CPAP group, with statistically significant differences (all P<0.05). Additionally, the CPAP group exhibited significantly lower scores in emotional responses and difficulties in emotion regulation across the same time points, with statistically significant differences (all P<0.05). In the non-CPAP group, increases in the apnea hypopnea index (AHI) and worsening emotional responses were key factors contributing to the exacerbation of depressive symptoms in OSA patients, with statistically significant differences (P<0.05). Conclusions CPAP therapy significantly improves depressive symptoms, emotional responses, and emotional regulation in OSA patients. Increases in the AHI and worsening emotional responses are primary factors leading to the worsening of depressive symptoms in OSA patients.
ObjectiveTo explore the correlation of serum neutrophil gelatinase-associated lipocalin (sNGAL) with inflammatory response in patients with community-acquired pneumonia (CAP) and assess the diagnostic value of sNGAL for severe CAP (SCAP).MethodsFrom January 2018 to June 2019, a total of 85 patients with CAP were enrolled in this study. Age, length of hospital stay, the levels of serum creatinine, blood urea nitrogen, white blood cell count,C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin, and CURB-65 score were compared between patients with SCAP (n=34) and patients without SCAP (n=51). The correlations of sNGAL with serum creatinine, blood urea nitrogen, white blood cell count, CRP, IL-6, procalcitonin, and CURB-65 score were assessed with Spearman’s correlation analysis. The area under the receiver operating characteristic (ROC) curve for sNGAL diagnosing SCAP was examined. ResultsCompared with patients without SCAP, SCAP patients demonstrated older age, longer hospital stay, higher serum CRP and IL-6 concentritions, and higher CURB-65 score (P<0.05). The Spearman’s correlation test showed that sNGAL was positively correlated with serum CRP, IL-6, PCT and CURB-65 score (rs=0.472, 0.504, 0.388, and 0.405, respectively; P<0.01). According to ROC analysis, the area under curve of sNGAL for diagnosing SCAP were 0.816, with a sensitivity of 76.56% and a specificity of 74.4% when the cut-off value was 171.0 ng/mL.ConclusionssNGAL concentration is positively correlated with the serverity of CAP. It can be regarded as a reliable indicator for diagnosis of SCAP in patients with CAP.
Objective To observe the characteristics of pattern electroretinogram (PERG) and the photopic negative response (PhNR) of flash electroretinogram (FERG) in patients and carriers with Leber hereditary optic neuropathy (LHON). MethodsA cross sectional, observational study. Thirty-two patients (64 eyes) diagnosed with LHON (LHON group) and 15 normal members with the same mutation in patient's family (carrier group) were included in this study from February 2021 to November 2021 in the Department of Ophthalmology of Renmin Hospital of Wuhan University. All patients in LHON group were males (100.0%, 32/32) and the average age was 23.34±7.41 years. In the carrier group of 15 cases (30 eyes), there were 2 males (13.3%, 2/15) and 13 females (86.7%, 12/15). The average age was 43.44±7.65 years. Twenty-four healthy subjects (48 eyes) in the same period were selected as the control group. Among them, there were 8 males (33.3%, 8/24) and 16 females (66.7%, 16/24). The average age was 23.42±2.54 years. All subjects were examined with the GT-2008V-VI visual electrophysiology instrument of Chongqing Gotec Medical Equipment Limited Company for PERG and FERG. P50 and N95 amplitudes of PERG and PhNR, a wave and b wave amplitudes of FERG were recorded. The peripapillary retinal nerve fiber layer (pRNFL) thicknesses of the nasal, superior, temporal, inferior and average quadrants were measured by spectral domain optical coherence tomography (SD-OCT). The amplitudes of a wave, b wave, PhNR, P50 wave, N95 wave and pRNFL thickness between the three groups were compared by one-way ANOVA. Pearson correlation analysis was used to analyze the correlation between different parameters. ResultsCompared with the control group, the amplitudes of PhNR in LHON group and carrier group decreased significantly (F=11.973, P＜0.001). The results of correlation analysis showed that the amplitude of PhNR in LHON group was significantly correlated with the thickness of nasal and temporal pRNFL (r=0.249, 0.272; P=0.048, 0.030). There was no significant difference in P50 wave amplitude between patients , carriers and controls (F=1.342, P=0.265). There was no significant difference in N95 wave amplitude between patients and controls (P=0.960). ConclusionThe PhNR amplitudes of FERG in LHON patients and carriers decrease significantly compared to controls.
