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@#MicroRNAs (miRNAs) are a class of short, highly conserved, non-coding RNA molecules that regulate gene expression by specific binding to the messenger RNAs (mRNAs). At present, the researches on miRNAs have caused immense global concern, and expression of miR-139-5p plays a significant role in tumorigenesis, metastasis and recurrence, through regulating proliferation, migration, and invasion of cancer cells in lung cancer, esophageal cancer, breast cancer, tongue squamous cell carcinoma, hepatocellular carcinoma, etc. MiR-139-5p has a positive impact on the prognosis of cancer, and it can combine with some chemotherapeutic drugs to reverse resistance and enhance the sensitivity of radiotherapy. It also works in the cells and tissues of other diseases, including nerve cells, and inflammation. This article reviewed the progress of miR-139-5p.
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Objective:To analyze the causes and risks of in-hospital death in geriatric patients with hip fracture.Methods:Retrospectively analyzed were the data of 1,878 elderly patients with hip fracture who had been admitted to Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from May 2015 to December 2017. There were 543 males and 1,335 females, with a male-to-female ratio of 1∶2.5 and a mean age of 79.6 years (from 65 to 105 years). There were 988 (52.6%) femoral neck fractures, 850 (45.3%) intertrochanteric fractures, and 40 (2.1%) femoral subtrochanteric fractures. 94.8% of the patients (1,781/1,878) received surgery. Cases of in-hospital death were recorded and their causes analyzed. The Estimation of Physiologic Ability and Surgical Stress (E-PASS) and the Nottingham Hip Fracture Score (NHFS) were used to assess the in-hospital deaths. The accuracy of these 2 assessment tools was validated on a small scale.Results:Thirteen in-hospital deaths were recorded, giving an in-hospital mortality of 0.69% (13/1,878). The direct causes of death were pulmonary infection in 7 cases, acute myocardial infarction in 2 cases, acute erosive hemorrhagic gastritis in 2 cases, acute respiratory distress syndrome in one, and suspected acute pulmonary embolism in one. Thirteen patients died, yielding a rate of in-hospital death of 5.3%±2.8% by E-PASS and that of 9.3%±4.0% by NHFS which were statistically different ( t=2.596, P=0.023). Conclusions:As geriatric patients with hip fracture are at a high risk of perioperative pulmonary infection, vigilance and early prevention are required during treatment. Care should be taken to monitor cardiovascular events and blood glucose, and stress ulcers should be prevented. The NHFS is recommended to assess the risks of in-hospital death in geriatric patients with hip fracture.
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Objective:To explore the epidemiological characteristics of patients with electrical burn at different voltages complicated by cerebral trauma, so as to provide a basis for improving the treatment level of such injury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 480 patients with electrical burn complicated by cerebral trauma treated in Qingdao Municipal Hospital affiliated to Qingdao University from January 2001 to December 2019. According to the voltage intensity, the patients were divided into low voltage group (injury voltage<1 kV, n=295) and high voltage group (injury voltage≥1 kV, n=185). Gender, age, status of burn and other general data of all patients were collected. The clinical manifestations, consciousness [Glasgow coma scale (GCS)], imaging findings, treatment, prognosis [Glasgow outcome scale (GOS)] and complications were compared between the two groups. Results:(1) Gender and age: the male to female ratio was 5.4∶1.0; the peak age of onset occurred at 18-60 years, accounting for 302 patients (62.9%); the status of burn: the burn area ranged from 1%-78% [(20.0±4.0)%] total body surface area (TBSA), with the current outlet located at the head in 321 patients. (2) Clinical manifestations: consciousness disorders accounted for the highest proportion, with 295 patients (100%) in low voltage group and 185 patients (100%) in high voltage group, followed by headache which occurred in 178 patients (60.3%) in low voltage group and 115 patients (62.2%) in high voltage group (all P>0.05). (3) Consciousness: 37 patients presented coma, with 17 patients (5.8%) in low voltage group and 20 patients (10.8%) in high voltage group ( P<0.05). (4) Imaging findings: CT and MRI examination found cerebral edema, skull fracture, intracranial hematoma, cerebral ischemia, subarachnoid hemorrhage, and other positive lesions. In patients with head wounds (current inlet and outlet located in the head), the incidence of cerebral trauma was 44.0% in low voltage group and 86.8% in high voltage group ( P<0.05). In patients with no head wound (the current outlet was not located in the head), the incidence of cerebral trauma was 5.3% in low voltage group and 6.3% in high voltage group ( P>0.05). In contrast with the patients without current outlet locating in the head, there were three more types of cerebral trauma in patients with current outlet locating in the head, including skull fracture, intracranial hematoma and subarachnoid hemorrhage. (5) Treatment, prognosis and complications: 478 patients (99.6%) received non-surgical treatment and 2 patients (0.4%) received surgical treatment. There was 1 death (0.2%) and 479 successfully treated patients (99.8%). The prognosis was good in 280 patients (94.9%), moderately disabled in 13(4.4%) and severely disabled in 2(0.7%) in low voltage group; while the prognosis was good in 143 patients (77.3%), moderately disabled in 30(16.2%), severely disabled in 11(5.9%) and death in 1(0.5%) in high voltage group (all P<0.01). After discharge, the incidence of numbness, paresthesia and anxiety was significantly higher in low voltage group than that in high voltage group (all P<0.01). Conclusions:Male patients with electrical burn complicated by cerebral trauma are more than female patients, with the young and middle-aged population being at high risk. Disturbance of consciousness and headache are the main clinical manifestations. The incidence of high voltage coma is relatively higher. Compared with low voltage-induced electrical burn, the patients with high voltage-induced electrical burn complicated by cerebral trauma (current inlet and outlet located at the head) sustain more severe and extensive injury. Early and active CT or MRI examination is conducive to definite diagnosis. Non-surgical treatment is the main treatment. Compared with high voltage-induced electrical burn, the patients with low voltage-induced electrical burn complicated by cerebral trauma have significantly better prognosis, but are more likely to develop complications of numbness, paresthesia and anxiety.
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Objective:To investigate the role and mechanism of exogenous derivative 4-octyl itaconate (4-OI) in lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods:C57BL/6 male mice were randomly divided into the control group, 4-OI group, LPS group, 4-OI+LPS group and deferiprone (DFP)+LPS group, with 6 mice in each group. LPS-induced ALI model was established by intraperitoneal injection of LPS. For the 4-OI+LPS group, mice were pretreated with 4-OI for 2 h before stimulation with LPS. The mice were sacrificed 12 h later and lung tissues were collected for pathological and molecular biological examination. Hematoxylin-eosin and Masson staining were used to detect the level of lung injury and collagen deposition. The expression levels of inflammatory cytokines and ferroptosis associated genes were detected by real-time quantitative PCR, and ferroptosis associated proteins were detected by Western blotting. The chi-square test was performed before the measurement data were counted. One-way analysis of variance was used to compare differences between multiple groups.Results:Compared with the control group, the histopathological damage was aggravated, and collagen deposition and lung injury score and lung wet-dry ratio were significantly increased in the LPS group (all P<0.05), and 4-OI pre-treatment significantly alleviated LPS-induced ALI. 4-OI treatment also significantly reduced the mRNA level of inflammatory cytokines, including IL-1β [(4.38±0.47) vs. (32.65±4.49)], IL-6 [(3.97±0.64) vs. (12.22±0.91)] and TNF-α [(15.06±2.26) vs. (38.53±2.31)]. At the same time, compared with the control group, the levels of lipid peroxidation metabolite 4-hydroxynonenal and malondialdehyde, iron level of lung tissue were significantly increased in the LPS group, and the mRNA level of ferroptosis marker prostaglandin-endoperoxide synthase 2 was also significantly increased (all P<0.05), but these indicators were significantly lower in the 4-OI+LPS group than in the LPS group. The results of immunofluorescence, Western blotting and PCR showed that the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and ferritin heavy chain (FTH1) significantly decreased in the LPS group, while 4-OI treatment significantly increased the Nrf2, GPX4 and FTH1 levels, and showed similar inhibition of ferroptosis with DFP (all P<0.05). Conclusions:4-OI attenuates LPS-induced ALI by increasing Nrf2 and upregulating FTH1 and GPX4, providing a potential drug and its theoretical mechanism for the prevention and treatment of ALI.
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Objective:To explore the targeted regulation of the inflammatory pathway and its mechanism after AMPK phosphorylation induced by lipopolysaccharide (LPS) in mice and human monocytes induced by THP-1, so as to provide evidence for the clinical application of Mogrol (MO) in the clinical treatment of acute lung injury.Methods:Twenty-four clean C57BL/6 male mice aged 6-8 weeks were randomly (random number) divided into the control group, MO group, LPS group and LPS+ MO group with 6 mice in each group. Mice in the control group were intraperitoneally injected with normal saline (30 mL/kg), mice in the MO group were intraperitoneally injected with MO (30 mg/kg), mice in the lipopolysaccharide group were intraperitoneally injected with lipopolysaccharide (10 mg/kg), mice in the lipopolysaccharide + MO group were intraperitoneally injected with MO (30 mg/kg), and the other side was injected with lipopolysaccharide (10 mg/kg) 30 min later. After 12 h, the mice were sacrificed for sampling and pathology and molecular biological tests were carried out. Cell experiment: THP-1 cells in good condition were cultured in RPMI 1640 medium containing 10% fetal bovine serum for 24 h, and then induced to differentiate into macrophages with 100 ng/mL PMA. The control group, MO group, LPS group and LPS + MO group were established. After drug stimulation, the cell suspension of each group was collected, and the cells and culture medium supernatants were used for subsequent detectionResults:Compared with the control group, the injury degree of the lipopolysaccharide group was obvious, the alveolar cavity structure was destroyed, the inflammatory cell infiltration was increased, and the alveolar septum was obviously thickened in the tissue sections. After MO intervention, the injury degree of lung tissue injury was greatly improved, and MPO and the lung wet/dry weight ratio were also significantly decreased. The mRNA levels of the inflammatory cytokines IL-1β, IL-6 and TNF- α in lung tissues were also significantly decreased under MO intervention [(2.96±0.10) vs. (5.53±0.14), (8.62±0.17) vs. (12.31±0.09), (3.01±0.09) vs. (4.85±0.36)]. The expression levels of NLRP3, caspase-1 p20, GSDMD-N and ASC in the lung tissues of mice in the lipopolysaccharide group were significantly higher than those in the control group, while the phosphorylation level of AMPK in the lipopolysaccharide + MO group was increased, and the expression of scorched death-related proteins was effectively inhibited [(0.58±0.09) vs. (0.89±0.15), (0.19±0.08) vs. (0.93±0.16), (0.65±0.09) vs. (0.86±0.14), (0.30±0.12) vs. (0.47±0.10), all P<0.05]. At the same time, the secretion of the inflammatory factors IL-1β and IL-18, the main markers of scorch death in the tissue measured by ELISA, could also be alleviated by MO. In the cell experiment, MO also promoted the phosphorylation of AMPK, inhibited the expression of proteins related to NLRP3 inflammatory bodies, and significantly improved cell viability. Conclusions:MO attenuates LPS-induced acute lung injury by inhibiting NLRP3-mediated cell pyrogenesis by promoting the phosphorylation of AMPK.
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Objective: To investigate the prevalence, awareness, treatment and control status of dyslipidemia among females aged ≥35 years old across China. Methods: Participants were selected by stratified multistage random sampling method in the "Twelfth Five-Year Plan" National Science and Technology Support Project "Survey on the Prevalence of Important Cardiovascular Diseases and Key Technology Research in China" project. This study is a retrospective, cross-sectional study. A total of 17 418 females aged 35 years and over were included in the current study. The basic information such as age, medical history and menopause was collected by questionnaire. The blood lipid parameters were derived from clinical laboratory examinations. The prevalence of dyslipidemia and the rate of awareness, treatment, and control of dyslipidemia were analyzed in females aged 35 years and over. Results: The age of participants was (56.2±13.0) years old, and the prevalence of dyslipidemia was 33.1% (5 765/17 418). The prevalence rates of high total cholesterol, hypertriglyceridemia, low HDL-C and high LDL-C were 9.7% (1 695/17 418), 11.1% (1 925/17 418), 10.9% (1 889/17 418) and 7.3% (1 262/17 418), respectively. The prevalence of dyslipidemia increased with age and the prevalence of dyslipidemia in women who were not married, Han, menarche age>16 years, obesity, central obesity, alcohol consumption, diabetes, hypertension and family history of cardiovascular disease were higher than those without such characteristics (P<0.05). There were 10 432 (59.9%) menopausal females in this cohort and prevalence of dyslipidemia of these participants was 38.8% (4 048/10 432), which was higher than that of non-postmenopausal females (24.6%, 1 717/6 986) (P<0.05). The awareness rates, treatment rates and control rates of dyslipidemia were 33.9% (1 953/5 765), 15.1% (870/5 765) and 2.5% (143/5 765) respectively among females aged 35 years and over in China. Conclusion: The prevalence of dyslipidemia in Chinese females aged 35 years and over is high, and its awareness, treatment, and control rates need to be optimized.
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Adult , Aged , Cardiovascular Diseases , China/epidemiology , Cross-Sectional Studies , Dyslipidemias/epidemiology , Female , Humans , Middle Aged , Obesity/epidemiology , Prevalence , Retrospective Studies , Risk FactorsABSTRACT
SARS-CoV-2, the pathogen of the COVID-19 pandemic, causes serious damage to human health and social stability. In severe COVID-19 cases, the infection triggers cytokine storm, resulting in multi-organ excessive inflammatory responses and even failure, which eventually leads to death. Recent studies have shown the activation of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays an essential role in the pathogenesis of COVID-19. SARS-CoV-2 can activate NLRP3 inflammasome through several pathways, thereby inducing the release of a large number of pro-inflammatory cytokines. This article reviews the activation of NLRP3 inflammasome caused by SARS-CoV-2 infection and the possible molecular mechanisms, and summarizes the progress in targeted inhibition of NLRP3 inflammation, aiming to provide a new strategy for the treatment of SARS-CoV-2 infection.
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Intestinal flora is the largest microbial community in human body， which consists of more than 1 000 species. Its structure and metabolites change dynamically with the age， diet and intestinal environment of the host. Study shows that the intestinal microbes play a pivotal role in regulating human physiological and pathological processes， and intestinal flora imbalance may be the key factors affecting the occurrence and development of bone and joint diseases， including osteoporosis， osteoarthritis， rheumatoid arthritis and gouty arthritis. At present， calcitonin， estrogen， nonsteroidal anti-inflammatory drugs， immunosuppressants， xanthine oxidase inhibitors and other western drugs are mostly used to treat the above diseases. However， long-term use of western drugs leads to poor compliance and obvious gastrointestinal adverse reactions among patients. Traditional Chinese medicine （TCM） predominates in the treatment of bone and joint diseases due to its low price， high efficacy and slight side effects， with the advantages of multi-targets， multi-mechanism and multi-levels. In recent years， many scholars have carried out experiments and clinical studies on the treatment of bone and joint diseases by TCMs on the basis of the liver and kidney theory such as "tonifying liver and kidney and strengthening muscles and bones". Gratifying results have been achieved. However， the mechanism of action has not been fully clarified. Intestinal flora becomes a hot spot in medical research， and a close relationship between intestinal flora and bone and joint diseases has been unveiled. Relevant literature in China and abroad showed that TCM has a significant effect on the treatment of bone and joint diseases by regulating intestinal flora. In this paper， the relationship between intestinal flora and bone and joint diseases was summarized and the intervention of TCM active ingredients and compounds on intestinal flora was reviewed to facilitate the prevention and treatment of bone and joint diseases by TCM.
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ObjectiveTo explore the possible mechanism of total flavonoids of peony flower （TFPF） in protecting rats from gouty nephropathy and provide data support for the pharmaceutical research on the treatment of gouty nephropathy. MethodGouty nephropathy rat model was established by adenine combined with ethambutol. Rats were randomly assigned into blank control group， model group， allopurinol （42 mg·kg-1） group， Tongfengshu tablets （600 mg·kg-1， positive control） group， and TFPF （260， 130， and 65 mg·kg-1） groups. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1 （MCP-1）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in rat serum and those of transforming growth factor-β1 （TGF-β1） and IL-1β in renal homogenate. Hematoxylin-eosin（HE） staining was carried out for observation of the morphological changes of renal cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） was conducted for observation of the DNA damage in renal cells. The expression of NOD-like receptor protein 3 （NLRP3）， cysteine aspartic acid protease（Caspase）-1 and IL-1β were observed by immunohistochemistry. The expression levels of NLRP3， Caspase-1 and nuclear transcription factor -κB （NF-κB） in renal tissues were detected by Western blot. ResultCompared with blank group， the contents of TNF-α， MCP-1， IL-1β， IL-18， and TGF-β1 in serum of model group were significantly increased （P<0.01）， and the expressions of NLRP3， Caspase-1， NF-κB and IL-1β in kidney of model group were significantly increased （P<0.01）. The renal tissue cells showed cytoplasmic swelling， cell membrane rupture， and the number of nuclear pyknotic fracture increased. The positive rate of TUNEL staining was significantly increased in model group （P<0.01）， and the contents of IL-1β and TGF-β1 in renal tissue homogenate were significantly increased （P<0.01）. Compared with model group， the contents of inflammatory factors TNF-α， IL-1β and IL-18 in serum of rats in TFPF high- and medium-dose groups could be decreased to different degrees （P<0.05， P<0.01）， while the content of MCP-1 in TFPF high-dose group was significantly decreased （P<0.01）. The content of TGF-β1 in renal tissue homogenate in TFPF high- and medium-dose groups was significantly decreased （P<0.05， P<0.01）， and the content of IL-1β in renal tissue homogenate in TFPF medium-dose group was significantly decreased （P<0.01）. HE staining showed that each dose group of TFPF could improve the status of renal tubular epithelial cells， reduce cytoplasmic swelling and the number of nuclear pyknosis to varying degrees. The positive rate of TUNEL staining was decreased （P<0.01） and DNA damage was decreased. The expression of NLRP3， Caspase-1， IL-1β and NF-κB protein in renal tissue cells was inhibited （P<0.05， P<0.01）. ConclusionTFPF protects rats from gouty nephropathy by inhibiting the secretion of inflammatory cytokines. Specifically， it may inhibit the activation of NF-κB and NLRP3/Caspase-1 pathways to reduce the expression， maturation， and release of inflammatory cytokines such as IL-1β and IL-18 and further inhibit pyroptosis， thereby reversing the inflammatory injury of kidney in gouty nephropathy.
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With the gradual aggravation of aging in China， the prevalence of osteoporosis is increasing year by year. Osteoporosis has become a major public health problem threatening the health of middle-aged and elderly people， especially middle-aged and elderly women. There are many predisposing factors and complex pathogenesis of osteoporosis. The interpretation of osteoporosis has been the focus of clinical research in recent years. How to prevent and treat osteoporosis more effectively has also become a major problem faced by researchers. In recent years， the balance and homeostasis of calcium and phosphorus regulated by intestinal absorption， renal excretion and bone have become one of the hot topics， and the balance and homeostasis of calcium and phosphorus in vivo are the key to normal bone homeostasis. At the same time， as a complex microbial community living in the gastrointestinal tract， intestinal flora can produce a variety of regulators affecting metabolism. It has been widely confirmed that it acts on the body indirectly or directly， in multiple ways and targets to prevent and treat osteoporosis. Therefore， further exploring the role and mechanism of intestine kidney bone axis in osteoporosis plays a far-reaching significance for the prevention and treatment of osteoporosis. In recent years， scholars have made a lot of exploration on the prevention and treatment of osteoporosis with traditional Chinese medicine （TCM）， and found that TCM can intervene the expression of intestinal flora and play the effect of prevention and treatment of osteoporosis. Based on the "intestine kidney bone axis"， this paper briefly discusses the integrated traditional Chinese and western medicine of kidney and osteoporosis， intestine and osteoporosis， intestine kidney axis， the treatment of kidney from intestine， intestine and osteoporosis， and the application of TCM in regulating intestinal flora in osteoporosis， in order to provide new ideas for the prevention and treatment of osteoporosis.
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With the gradual aggravation of aging in China， the prevalence of osteoporosis is increasing year by year. Osteoporosis has become a major public health problem threatening the health of middle-aged and elderly people， especially middle-aged and elderly women. There are many predisposing factors and complex pathogenesis of osteoporosis. The interpretation of osteoporosis has been the focus of clinical research in recent years. How to prevent and treat osteoporosis more effectively has also become a major problem faced by researchers. In recent years， the balance and homeostasis of calcium and phosphorus regulated by intestinal absorption， renal excretion and bone have become one of the hot topics， and the balance and homeostasis of calcium and phosphorus in vivo are the key to normal bone homeostasis. At the same time， as a complex microbial community living in the gastrointestinal tract， intestinal flora can produce a variety of regulators affecting metabolism. It has been widely confirmed that it acts on the body indirectly or directly， in multiple ways and targets to prevent and treat osteoporosis. Therefore， further exploring the role and mechanism of intestine kidney bone axis in osteoporosis plays a far-reaching significance for the prevention and treatment of osteoporosis. In recent years， scholars have made a lot of exploration on the prevention and treatment of osteoporosis with traditional Chinese medicine （TCM）， and found that TCM can intervene the expression of intestinal flora and play the effect of prevention and treatment of osteoporosis. Based on the "intestine kidney bone axis"， this paper briefly discusses the integrated traditional Chinese and western medicine of kidney and osteoporosis， intestine and osteoporosis， intestine kidney axis， the treatment of kidney from intestine， intestine and osteoporosis， and the application of TCM in regulating intestinal flora in osteoporosis， in order to provide new ideas for the prevention and treatment of osteoporosis.
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Over the last decade, clinical trials using various poly ADP ribose polymerase (PARP) inhibitors on patients with ovarian cancer have shown promising results. The introduction of PARP inhibitors has changed the treatment landscape and improved outcomes for patients with ovarian cancer. Fuzuloparib, developed by Jiangsu Hengrui Pharmaceuticals Co., Ltd., is a novel orally available small molecule PARP inhibitor. By introducing the trifluoromethyl group into chemical structure, fuzuloparib exhibits higher stability and lower inter-individual variability than other PARP inhibitors. Several clinical trials (FZOCUS series and others) have been carried out to assess the efficacy and safety of fuzuloparib through different lines of treatments for advanced or recurrent ovarian cancer in both treatment and maintenance. Here, we present the most recent data from these studies, discuss current progress and potential future directions.
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Cells are in complicated mechanical and physical microenvironment in vivo. The former mainly includes flow shear, tension, compression or torsion, and the latter covers stiffness and topography of extracellular matrix, spatial location, volume constraint or osmotic pressure, featured with various types, patterns, and parameters of mechanical or physical loading. Cell biomechanics mainly focuses on the alteration of mechanical properties of cells and the mechanical remodeling of subcellular components, the cell development, growth, proliferation, differentiation, and apoptosis under distinct mechanical stimuli, and the cellular sensation, transmission, transduction, and responses to external forces. This review summarized the major progresses in cell biomechanics in 2021, including studies on cardiomyocytes, endothelial cells, osteoblasts, immune cells, cancer cells and stem cells, as well as the related new techniques.
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Objective:To explore the effects and mechanism of apigenin on lung ischemia-reperfusion (I/R) injury in mice.Methods:A total of 40 male C57/B6 mice were randomized into 4 groups of sham, I/R, low-dose apigenin and high-dose apigenin (n=10 each). Lung I/R injury model was established by clipping left hilum for 1h and reperfusion for 2 h. Low/high-dose apigenin group received a gavage of apigenin (10/50 mg·kg -1·d -1) for 7 days before lung I/R.After 2-hour reperfusion, lung tissue was collected and lung injury status evaluated and scored by hematoxylin-eosin (H&E) stain; mRNA expression levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), high mobility group box 1 (HMGB1), prostaglandin-endoperoxide synthase 2 (PTGS2) and glutathione peroxidase 4 (GPX4) were detected by reverse transcription-polymerase chain reaction (RT-PCR); Western blot was utilized for detecting the protein expressions of Bax, Bcl-2 and HIF-1α.Finally, after morinostat activated Hif-1α, the effect of apigenin (50 μmol/L) on hypoxia-reoxygenation (H/R)-induced ferroptosis was further observed in A549 lung epithelial cells. Results:As compared with sham group, lung injury score spiked markedly in I/R group (7.05±0.6 vs.1.25±0.42), pulmonary edema worsened obviously (8.65±1.12 vs.4.17±0.54), the percentage of Tunel positive cells rose significantly (58.22±4.92 vs.8.23±1.22) and mRNA expression levels of IL-1β, TNF-α and HMGB1 increased (7.82±0.16 vs.1.00±0.14, 4.24±0.12 vs.1.00±0.19, 6.24±0.19 vs.1.00±0.11) ( P<0.05); Compared with I/R group, lung injury score declined markedly in low/high-dose apigenin group (4.88±0.31/2.11±0.29 vs.7.05±0.66)( P<0.05), pulmonary edema lessened markedly (6.42±1.03/4.88±1.62 vs.8.65±1.12)( P<0.05) and the percentage of Tunel positive cells (41.46±6.73/16.02±5.31 vs.58.22±4.92) and the mRNA expression levels of IL-1β, TNF-α and HMGB1 became obviously suppressed (5.88±0.13/3.21±0.19 vs.7.82±0.16, 3.56±0.11/2.12±0.09 vs.4.24±0.12, 4.12±0.14/3.12±0.09 vs.6.24±0.19)( P<0.05); protein expressions of HIF-1α and PTGS2 dropped sharply in low/high-dose apigenin group (2.00±0.10/0.93±0.11 vs.2.99±0.06, 4.12±0.14/2.51±0.18 vs.6.11±0.12) while GPX4 protein rose obviously (0.55±0.02/0.83±0.02 vs.0.38±0.04)( P<0.05). In vitro experiments further showed that apigenin could significantly suppress the H/R-induced protein expression of PTGS2 in A549 lung epithelial cells (1.11±0.0 vs.4.55±0.12)( P<0.05) while up-regulating the protein expression of GPX4 (0.93±0.11 vs.0.32±0.04)( P<0.05). The inhibition of PTGS2 protein (4.01±0.12 vs.1.11±0.05) and the up-regulation of GPX4 were significantly blocked (0.52±0.05 vs.0.93±0.11)( P<0.05). Conclusions:Through an inhibition of HIF-1α/ferroptosis axis, apigenin can alleviate lung injury, apoptosis and inflammatory response associated with lung I/R in mice.
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Objective:To study the impact and the mechanism of splenectomy combined with pericardial devascularization on cirrhotic livers.Methods:Serum samples and clinical data were collected preoperatively and postoperatively from 54 patients with cirrhosis who underwent splenectomy combined with pericardial devascularization from May 2013 to Oct 2014 at Beijing You’an Hospital, Capital Medical University. Changes in hepatic arterial and portal venous blood flow, liver function and fibroscan results were analyzed. The levels of nitric oxide (NO), endothelin-1 (ET-1), interleukin-6 (IL-6), hepatocyte growth factor (HGF), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 1 (MMP1) were measured.Results:There were 31 males and 23 females, aged(45.48±10.21)years. Free portal vein pressure decreased significantly from (37.0±7.1) cmH 2O (1 cmH 2O=0.098 kPa) to (26.1±5.7) cmH 2O after surgery ( P<0.05). Significant increases in postoperative lumen diameter (4.0±1.0) mm vs (3.1±0.7) mm were observed, accompanied by increase in peak flow velocity and blood flow of the hepatic artery. Significant deductions in lumen diameter (11.9±2.0) mm vs (13.1±1.9) mm, accompanied by reduction of peak flow velocity and blood flow of the portal vein were observed following surgery (all P<0.05). The NO level was significantly elevated immediately after splenectomy and was subsequently remained at high levels. The ET-1 level decreased 2 days after surgery and became fluctuated at low levels. The IL-6 and HGF levels increased significantly 2 days after surgery and decreased gradually after 7 days and 1 month, respectively. The TGF-β1 and the MMP1 levels increased after surgery. The endotoxin level decreased significantly after surgery (all P<0.05). Conclusion:Splenectomy combined with pericardial devascularization induced hepatic blood flow restoration, hepatocyte regeneration and reversal of fibrosis in cirrhotic livers. Splenectomy has a protective effect on cirrhotic liver when combined with pericardial devascularization.
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Objective:To evaluate the effect of apneic oxygen insufflation (AOI) on phenotypic transformation of alveolar macrophage (AM) in the non-ventilated lung during one-lung ventilation (OLV).Methods:A total of 60 patients of either sex, aged 40-64 yr, weighing 45-85 kg, undergoing elective thoracoscopic lobectomy, were recruited and divided into 2 groups using a computer-generated table of random numbers: test group and control group, with 30 cases in each group.At the beginning of OLV, the non-ventilated lung received 3 L/min of AOI in test group and no AOI in control group.Radial artery blood samples were collected for blood gas analysis before operation, immediately after anesthesia induction, 30 min, 1 h and 2 h after the start of OLV, and oxygenation index (OI) was calculated.The resected normal lung tissues around the lung lobe were excised at 2 h after the start of OLV for microscopic examination of the pathological changes after HE staining, and the lung injury score was assessed.Bronchoalveolar lavage fluid (BALF) was collected at 2 h after the start of OLV, AM was sorted by flow cytometry, and the apoptotic rate was calculated.The levels of intracellular Ca 2+ and reactive oxygen species (ROS, a marker of M1 AM phenotype) in cells were determined.The concentrations of M1 phenotype AM markers inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) and of M2 phenotype AM markers arginase 1 (Arg-1) and interleukin 10 (IL-10) in BALF were measured by enzyme-linked immunosorbent assay. Results:Compared with control group, SpO 2, PaO 2 and OI were significantly increased, PaCO 2 and lung injury score were decreased, the survival rate of AM was increased, the apoptotic rate in the early and late stages was decreased, the concentrations of iNOS, IL-6 and TNF-α in BALF were decreased, and the concentrations of Arg-1 and IL-10 in BALF were increased, the level of ROS in AM was decreased, and the level of Ca 2+ in AM was increased in test group ( P<0.05). Conclusions:The mechanism by which implementing AOI in the non-ventilated lung reduces lung injury may be related to promotion of transformation of AM from M1 phenotype to M2 phenotype and inhibition of inflammatory responses during OLV in the patients undergoing thoracoscopic lobectomy.
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Previous studies believe that oligometastasis has unique biological characteristics. Early active treatment for patients with oligometastatic prostate cancer can delay disease progression and improve survival. However, the current definition of oligometastasis is still unclear, and its optimal treatment is still a major concern of the medical community. This article reviewed recent research progresses in term of the definition and comprehensive treatment strategy of oligometastatic prostate cancer.
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Objective:To explore new methods of treating Graves′ disease (GD) by targeting thyroid stimulating hormone receptor (TSHR) and intercellular adhesion molecule-1 (ICAM-1).Methods:The small interfering RNA (siRNA) targeting TSHR and the ICAM-1 monoclonal antibody (mAb) were designed and synthesized. Thirty GD model mice were randomly divided into siRNA treatment group, ICAM-1 mAb treatment group, and untreated GD group (10 mice in each group), and 10 normal mice were taken as blank control. Serum thyroxine (T 4), thyroid stimulating hormone (TSH), TSH receptor-stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb) were measured before and after treatment. At the end of the treatment, body mass and heart rate of mice in each group were measured, and thyroid uptake of 99Tc mO 4-, thyroid size and pathological changes were evaluated. Independent-sample t test, paired t test and one-way analysis of variance were used to analyze data. Results:After three treatments, the body mass of mice in siRNA group and ICAM-1 mAb group were significantly lower than that of normal mice ( F=3.50, P=0.025); the heart rates of the mice in two groups were significantly lower than that of untreated GD mice ( F=24.73, P<0.001). Heart rate of mice treated with siRNA decreased significantly, close to that of normal mice. After treatment, the serum T 4((27.58±1.94) vs (65.71±6.89) μg/L, (27.24±3.50) vs (70.84±8.46) μg/L), TSAb ((331.44±43.38) vs (457.33±45.85) mU/L, (275.16±45.80) vs (443.91±42.32) mU/L) and TSBAb ((13.94±1.11) vs (15.83±5.92) mU/L, (14.59±1.02) vs (17.05±6.16) mU/L) levels of mice in both siRNA group and ICAM-1 mAb group significantly decreased ( t values: 4.45-10.87, all P<0.05), while the serum TSH levels of mice in two groups significantly increased ((0.13±0.05) vs (0.04±0.05) mU/L, (1.46±0.34) vs (0.06±0.03) mU/L; t values: -2.22, -5.87, P values: 0.007, <0.001). The elevated TSH level and decreased TSAb level of mice treated with ICAM-1 mAb were significantly different from those treated with siRNA ( t values: 1.03, -1.63, P values: 0.002, 0.031). After treatment, the uptake of 99Tc mO 4- in part of the thyroid lobes of mice was decreased, and the enlargement degree of the corresponding lobes was reduced. The thyroid pathology of mice in the treated groups showed that the absorption vacuoles of thyroid follicles were reduced, and the phenomenon of thinner colloids was improved. No obvious damage was observed in the heart, liver and kidneys of the mice. Conclusions:Both the siRNA targeting TSHR and ICAM-1 mAb have therapeutic effects on GD model mice. The siRNA is better at controlling heart rate, and ICAM-1 mAb is better at increasing TSH and decreasing TSAb. Each of the above treatment methods is safe and effective, which can provide new ideas for GD targeted therapy.
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Objective:To evaluate the safety and validity of enriched autologous bone marrow mesenchymal stem cells (BMSCs) and annular suture for repairing defect after lumbar discectomy.Methods:Enrichment of autologous BMSCs: autologous bone marrow blood was collected from 5 patients undergoing lumbar surgery, and nucleated cells were enriched on gelatin sponge particles by selective cell retention technique. From October 2016 to March 2019, 109 patients with lumbar disc herniation underwent discectomy with mobile microendoscopic discectomy technique, including 61 males and 48 females, aged 24-59 years. Discectomy group: 26 cases received simple discectomy. Suture group: 39 cases received annular suture after discectomy. BMSCs+suture group: 44 cases received intradisc transplantation of gelatin sponge particles enriched with autologous BMSCs and annular suture after discectomy. The perioperative conditions were recorded, with visual analogue scale (VAS), Oswestry dysfunction index (ODI), Pfirrmann grade of disc degeneration, disc height and degree of herniationevaluated after operation.Results:In enrichment test with flow cytometry, the enrichment multiple of nucleated cells and target cells was 6.4±0.9 and 4.2±0.6 respectively, and BMSCs grew well in vitro. The operation time was 35-55 mins. 7 cases in the suture group were transferred to the discectomy group and 10 cases in the BMSCs+suture group were transferred to BMSCs group due to unsuccessful suture. There were no significant differences in VAS, ODI, Pfirrmann grade of disc degeneration, disc height and degree of herniation among the groups. There was no significant difference in intraoperative bleeding, postoperative drainage and length of hospital stay. The incision was healed without redness and swelling. 18 patients were followed up for 6 months, and 91 cases were followed up for 1-3 years (25.0±5.6 months). There was no interbody fusion, heterotopic ossification or infection during follow-up. VAS and ODI decreased significantly after operation in all patients. At final follow-up, the VAS improvement rate of BMSCs+suture group (81.7%±7.9%) was higher than discectomy group (73.0%±8.9%), suture group (74.0%±6.9%) and BMSCs group (75.3%±8.4%); the ODI improvement rate of BMSCs+suture group (91.9%±8.8%) was higher than discectomy group (86.2%±8.1%) and suture group (86.4%±5.5%). According to MRI, the Pfirrmann grade of disc increased 0.7 in discectomy group, 0.6 in suture group, while it did not increased significantly in BMSCs+suture group and BMSCs group, and the progress of Pfirrmann grade in BMSCs+suture group and BMSCs group were lighter than discectomy group and suture group.The disc height decreased in each group, the loss rate of disc height in BMSCs+suture group (17.2%±4.3%) was less than discectomy group (29.3%± 6.3%) and suture group (20.6%±5.7%); and suture group was less than discectomy group. The degree of herniation was reduced by more than 50% in all groups, while 1 case in discectomy group had herniation without clinical symptoms.Conclusion:Autologous BMSCs and annulus suture are safe and effective in repairing the defect after lumbar discectomy, which may help to slow down the degeneration of intervertebral disc.
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Objective:To evaluate the value and efficacy of microscope-assisted minimally invasive anterior lumbar discectomy and zero-profile fusion (ALDF) for lumbar degenerative diseases.Methods:Anterior lumbar distractors were designed to maintain the distraction of intervertebral space and expose the posterior edge of the intervertebral space. From June 2018 to December 2020, 41 cases of lumbar degenerative diseases were treated with this operation, including 19 men and 22 women, aged 29-71 years old (average 42.1 years old). All patients had intractable low back pain. Imaging examination showed lumbar disc degeneration with narrow intervertebral space, including disc herniation with Modic changes in 7 cases, spinal stenosis with instability in 16 cases and spondylolisthesis in 18 cases. The involved levels included L 2,3 in 1 case, L 3,4 in 3 cases, L 2-L 4 in 1 case, L 4,5 in 17 cases and L 5S 1 in 19 cases. An incision was taken that was pararectus for L 2-L 4 and transverse for L 4-S 1, with the intervertebral disc exposed via extraperitoneal approach. The intervertebral space was released and distracted after discectomy in intervertebral space, and self-made distractors were used to maintain the space. Under microscope, the herniation, posterior annulus and osteophyte were removed for sufficient decompression, with a suitable self-anchoring cage implanted into the intervertebral space. The visual analogue score (VAS), Oswestry dysfunction index (ODI), intervertebral space height, lordosis angle and spondylolisthesis rate were evaluated. Results:Operations were performed successfully in all the patients. The operation time was 70-120 min with an average of 90 min, and the intraoperative blood loss was 15-70 ml with an average of 30 ml. No severe complication such as nerve or blood vessel injury occurred. The patients were followed up for 12 to 36 months, with an average of 18 months. At the last follow-up, VAS decreased from 6.4±2.3 to 1.1±0.9, and ODI decreased from 44.9%±16.9% to 5.8%±4.7%. Intervertebral space height recovered from 7.2±2.8 mm to 12.1±2.1 mm and lordosis angle recovered from 6.9°±4.8° to 10.1°±4.6°. X-ray showed significant recovery of intervertebral space height, lordosis angle and spondylolisthesis rate, with obvious interbody fusion and no displacement of cage. For 18 patients of spondylolisthesis, the slippage recovered from 16.6%±9.3% to 7.6%±5.3%, with an average improvement of 54.2%.Conclusion:Microscope-assisted minimally invasive ALDF can provide sufficient decompression and zero-profile fusion for lumbar degenerative diseases with satisfactory results during short-term follow-up.