Intestinal tract is the largest immune organ of human body where hundreds of millions of microorganisms are colonized which are called intestinal flora. Each intestinal flora checks and balances each other, depends on and complements each other, and forms a mutually beneficial symbiotic relationship with the host. Changes in quantity and type of intestinal flora will cause the imbalance of intestinal microecology, affect the systemic immune function through immune regulation, and then affect the progress of the disease. At present, it has been found that intestinal microecology is closely related to rheumatic immune diseases such as systemic lupus erythematosus, ankylosing spondylitis, gouty arthritis and rheumatoid arthritis. Taking intestinal flora as the starting point to explore the pathogenesis of gout has become a new research hotspot. Based on the current research, the relevant literature was consulted in present paper, and the intestinal microecological composition and function, the structural characteristics of intestinal flora in patients with gout, the mechanism of intestinal flora in the pathogenesis of gout, and the treatment of probiotics, traditional Chinese medicine and fecal microbial transplantation were reviewed, in order to provide new ideas and directions for prevention and treatment of gout in the future.

Infection is a common complication and leading cause of death in liver cirrhosis patients. In recent years, people gradually recognize the vital impact of infection, especially spontaneous bacterial peritonitis, on the course and prognosis of liver cirrhosis patients. Timely and effective empiric antibiotic therapy is particularly critical for the treatment of liver cirrhosis patients with bacterial infection. However, due to the spread of multidrug resistant bacteria and extensively drug-resistant bacteria, infection in cirrhosis has also become a difficult problem. At the same time, we have a clearer understanding on the pathogenesis of infection in cirrhosis. Novel therapeutic methods, such as intestinal microecological intervention and immunoregulatory therapy, have also become research hotspots recently. Establishing an effective treatment plan for liver cirrhosis patients with bacterial infections is the key to improve the survival rate and quality of life of these patients.

Liver cirrhosis is the end stage of chronic liver diseases with various complications, thereby imposing great burden to the patient's family and public health care. Abnormal nutritional status, mainly including malnutrition and overnutrition(overweight/obesity), are related to the occurrence of many chronic liver diseases, and have major impact on the progression and outcome of liver cirrhosis. Nutritional status of cirrhotic patients should be comprehensively assessed based on various factors, including underlying diseases, diet, clinical manifestations, and laboratory tests, etc. Cirrhotic patients with malnutrition should receive individualized nutritional support therapy in timely fashion, and those with overweight/obesity should undergo dietary intervention or physical activity to improve the quality of life and reduce the risk of death.

Objective To explore the effect of miR-491-5p on the apoptosis of trophoblast cells induced by hypoxia and the process of preeclampsia. Methods Human trophoblast cells were divided into control group, hypoxia group, hypoxia+miR-491-5p mimic group and hypoxia+miR-491-5p inhibit group. Cell viability staining was used to detect hypoxia-induced trophoblast cell apoptosis. qRT-PCR was used to detect the expression of miR-491-5p in hypoxia-induced trophoblast cells; TargetScan database to predict miR-491-5p target; Detection of dual-luciferase reporter gene was used to confirm the targeting relationship between miR-149-5p and BCL2l2; miR-491-5p mimic and inhibitor single-stained embryonic trophoblast cells, qRT-PCR was used to detect the expression of miR-491-5p. Western blotting was used to detect changes of BCL2l2 expression in trophoblast after overexpression and inhibition of miR-491-5p; cell viability staining, Western blotting, and flow cytometry to detect trophoblast apoptosis. Results Compared with control group, the hypoxia group had significantly increased cell apoptosis and increased expression of miR-491-5p (2.784±0.214 vs. 1.000±0.000, P<0.01); bioinformatics detection and dual luciferase detection report experiments showed that miR-491-5p can targete and regulate BCL2l2 expression. Compared with control group, the miR-491-5p content in hypoxia+miR-491-5p mimic group was significantly increased (7659.300±191.300 vs. 5.467±0.503, P<0.05), while that in miR-491-5p inhibit group was the opposite (0.139±0.022 vs. 0.323±0.035, P<0.01). Compared with hypoxia group, the apoptosis rate of trophoblast cells was decreased (11.56%±0.452% vs. 16.67%±0.750%, P<0.01), the expressions of BCL2L2 (0.702±0.047 vs. 0.312±0.007, P<0.001) and Bcl-2 (0.752±0.055 vs. 0.415±0.005, P<0.01) were increased, and the expression of Bax (1.221±0.066 vs. 1.652±0.085, P<0.01) was decreased in hypoxia+miR-491-5p inhibit group; but in hypoxia+miR-491-5p mimic group, the apoptosis rate was increased (23.54%±1.233% vs. 16.67%±0.750%, P<0.001), the contents of BCL2L2 (0.211±0.013 vs. 0.312±0.007, P<0.01) and Bcl-2 (0.203±0.011 vs. 0.415±0.005, P<0.001) was decreased, and Bax (2.362±0.284 vs. 1.652±0.085, P<0.01) expression was increased. Conclusions miR-491-5p might negatively regulates the expression of BCL2L2, increases the apoptosis of trophoblast cells induced by hypoxia and accelerates the development of preeclampsia.

Objective To investigate the effect and mechanism of Paris saponins on iron death in triple negative breast cancer cells. Methods MDA-MB-231 cells were treated with 0, 10, 20, 30, 40 and 50 μmol/L of Paris saponins. Cell viability was detected by CCK-8 method. MDA-MB-231 cells at logarithmic growth stage were randomly divided into control group, Paris saponin group (treated with 30 μmol/L Paris saponin for 12 h), inhibitor group (treated with 2 μmol/L Ferrostatin for 12 h) and Paris saponin + inhibitor group (treated with 30 μmol/L Paris saponin for 12 h after treatment with 2 μmol/L Ferrostatin-1 for 12 h), cell viability was detected by CCK-8 method, cell apoptosis rate was detected by flow cytometry. The expressions of divalent metal ion transporter 1 (DMT1), transferrin receptor 1 (TFR1), glutathione peroxidase 4 (GPX4), p53 and p53/SLC7A11 were detected by qRT-PCR and Western blotting. Results CCK-8 assay showed that the survival rate of MDA-MB-231 cells was decreased with the increase of the concentration of Paris saponin in a dose-dependent manner (P<0.05). Compared with control group, the cell survival rate, the relative expression levels of CPX4, SLC7A11 mRNA and protein decreased, while of apoptosis rate, the relative, expression levels of TFR1, DMT1, p53 mRNA and protein increased in Paris saponin group, the relative expression levels of CPX4, SLC7A11 mRNA and protein increased in inhibitor group, the apoptosis rate and the relative expressions of TFR1, DMT1 and p53 mRNA and protein were decreased (P<0.05). Compared with inhibitor group, the cell survival rate and the mRNA and protein relative expressions of CPX4 and SLC7A11 decreased, while the apoptosis rate and the mRNA and protein relative expressions of TFR1, DMT1 and p53 increased in parisaponin + inhibitor group (P<0.05). Conclusion Paris saponin inhibits the proliferation of triple negative breast cancer cells and promotes iron death in cancer cells, possibly through the regulation of p53/SLC7A11 signal axis.

Objective By literature review to retrospectively study the clinical characteristics, diagnosis and treatment process, and prognosis of anti-melanoma differentiation associated gene 5 (MDA5) autoantibody-positive dermatomyositis-associated with interstitial lung disease (ILD) treated with tofacitinib (TOF), so as to improve the understanding of the disease. Methods Retrospectively analyze the clinical and laboratory characteristics, imaging findings and adverse reactions before and after TOF treatment in seven patients who admitted to the First Medical Center of Chinese PLA General Hospital from January 2018 to October 2021. Thirty-six cases were found by searching databases to summarize the efficacy and safety of TOF in treating patients with anti-MDA5 autoantibody-positive dermatomyositis-associated ILD. Results Of the 7 patients, 5 were female and 2 were male with mean age of 50(30-64) years, the mean disease duration was 3(1-36) months, and the mean follow-up time was 12(1-35) months. Of them, 4 received previously the other immunosuppressive therapy, and 3 were newly treated. One patient died, and the remaining 6 patients were in relatively stable condition and maintenance treatment. One patient experienced fungal infection in the 18th month after TOF treatment. A total of 36 cases of anti-MDA5 autoantibody-positive dermatomyositis have been reported in databases. Clinical symptoms, laboratory tests and imaging findings were all improved after TOF therapy. Opportunistic infection occurred in 9(25%) cases after application of TOF. Conclusion Application of TOF is an effective and safe regimen in treatment of anti-MDA5 autoantibody-positive dermatomyositis-associated ILD, while attention should be paid for monitoring the opportunistic infection during treatment.

Antithrombotic drugs are important means to prevent and treat thrombotic diseases. With the wider use of antithrombotic drugs, the incidence of antithrombotic drug-related bleeding has increased year by year. Anticoagulant drugs, antiplatelet drugs and thrombolytic drugs can all cause subcutaneous hemorrhage, gastrointestinal hemorrhage and even intracranial hemorrhage, resulting in death or disability. Therefore, the Chinese Society of Thrombosis, Hemostasis and Critical Care organized multidisciplinary experts to jointly write this specification to help clinicians regulate the treatment of antithrombotic drug-related bleeding. This specification includes four parts: antithrombotic drug monitoring, bleeding evaluation, reversal treatment and restart of antithrombotic treatment.

Objective To investigate the role and mechanism of neutrophil extracellular traps (NETs) in acute liver injury from heatstroke (HS) mouse model. Methods Fifty-six C57BL/6 mice were randomly (random number table) assigned into sham heated control group (control group, n=8), sham heated with Chlorine amidine (CA) treatment group (CA group, n=8), heatstroke group (HS, n=32), and heatstroke with CA treatment group (HS+CA, n=8). In the HS group, after heat-shock treatment, mice were further subgrouped into HS 0 h, HS 3 h, HS 6 h, and HS 9 h (n=8/subgroup). Another forty-eight mice were randomized into the control group, CA group, HS(9 h) group, and HS+CA group (n=12/group). We tracked the survival rate of these mice up to 216 h. Mice were prepared with the pre-warm chamber to initiate HS. The change in rectum temperature (Tr) was monitored and the time point reaching 42.9 ℃ was recorded. At the end of heat stress, the mice were sacrificed according to the group time point, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured by the automatic biochemical analyzer. HE staining was used to observe the pathological injury of liver tissue. Plasma-free DNA and myeloperoxidase (MPO)-DNA complex concentrations were detected by the kit. The expression of citrullinated histone (Cit H3) and MPO in liver tissue was observed by a laser confocal microscope. The concentration of IL-1β in liver tissue homogenate was determined by ELISA.The activation level of Nlrp3 inflammasome in liver tissue was detected by Western blotting. Results There was no significant difference in heat exposure time and core body temperature rise rate between HS+CA group and HS group at the end of heat shock(P>0.05), but the survival time of HS+CA group was longer than that of HS group (P<0.05). At 3 h, 6 h, and 9 h after heat shock, the activities of serum ALT and AST, and the pathological scores of liver tissue increased progressively with time and were significantly higher than those in control group (P<0.001). At 3 h, 6 h, and 9 h after heat shock, the concentrations of plasma-free DNA and MPO-DNA, the levels of Cit H3 and MPO in liver tissue increased progressively with time and were significantly higher than those in control group (P<0.001). HE staining of liver tissue showed that, compared with HS group, the degeneration of hepatocytes in HS+CA group was significantly alleviated, inflammation was significantly alleviated, and there was little blood stasis in hepatic sinuses without bleeding. Inhibition of NETs release significantly alleviated heat stress-induced liver injury (HS+CA group vs. HS 9 h group, P<0.001). Survival analysis showed that the survival rate of mice in HS+CA group was higher than that in HS group (χ²=4.719,P<0.05). The expression levels of Nlrp3 and cleaved caspase-1 and IL-1β in liver tissue of HS+CA group were lower than those in HS group (P<0.001). Conclusion NETs may play an important role in the pathogenesis of HS liver injury through the Nlrp3 inflammasome/IL-1β signal pathway.

Objective To explore the effect and mechanism of silybin on improving pulmonary fibrosis and oxidative stress in mice. Methods A total of 120 mice were randomly divided into sham operation group, lung injury model group, dexamethasone group, low-dose, medium-dose and high-dose silybin groups (20 mice each). The models of pulmonary injury mice were induced by bleomycin. Mice in dexamethasone group, low-, medium- and high-dose silybin groups were given intragastric administration of dexamethasone (3 mg/kg) and silybin (120, 240, 480 mg/kg), while sham operation group and lung injury model group were given the same volume of normal saline for 28 d. The bronchoalveolar lavage fluid (BALF) and pulmonary tissues of each group were collected. The count of inflammatory cells in BALF was examined by microscopy. The pathological damage of pulmonary tissues was observed by HE staining. The pulmonary wet/dry weight ratio (W/D) was detected by wet-dry weighting method. The content of hydroxyproline (HYP) in pulmonary tissues, and levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in BALF were detected by ELISA. The expressions of bone morphogenetic protein 9 (BMP9)/bone morphogenetic protein receptor 2(BMPR2)/SMAD signaling pathways-related proteins were detected by Western blotting. Results Compared with sham operation group, count of BALF inflammatory cells, scores of pulmonary injury and fibrosis, W/D, HYP, and MDA, TNF-α, IL-1β and IL-6 levels in BALF increased significantly, while SOD, GSH-Px activity, T-AOC levels in BALF, as well as the relative expression levels of BMP9, BMPR2 and p-SMAD1/5/9 in lung tissues decreased significantly in lung injury model group (P<0.05). Compared with lung injury model group, count of BALF inflammatory cells, scores of pulmonary injury and fibrosis, W/D, HYP, and MDA, TNF-α,IL-1β and IL-6 levels in BALF decreased significantly, while SOD, GSH-Px activity, T-AOC level in BALF, and BMP9, BMPR2 and p-SMAD1/5/9 expression levels in lung tissues increased significantly in high-dose silybin group and dexamethasone group(P<0.05). Conclusion The silybin may improve bleomycin-induced pulmonary fibrosis and oxidative stress in lung injury mice by mediating BMP9/SMAD signaling pathways, and thereby repairing pulmonary injury.

Chronic obstructive pulmonary disease (COPD) is a common pulmonary disease in elderly, in which the pulmonary respiratory mechanics has gradually changed, while surgery, general anesthesia and conventional mechanical ventilation will seriously affect the pulmonary respiratory mechanics of COPD patients, which are more likely to have severe perioperative pulmonary complications. Therefore, according to the features of the respiratory mechanics of COPD patients and the characteristics of changes in respiratory mechanics during mechanical ventilation, to select individualized ventilation strategies to improve their respiratory mechanics and apply different monitoring methods to optimize the interaction between human and ventilator during ventilation of COPD patients for achieving the purpose of lung protection are very important for patients with COPD during the perioperative period. This review describes in detail the physiological status of the patients with COPD patients and the characteristics of respiratory mechanics during mechanical ventilation, and through the summary and discussion of recent literature, describes different ventilation strategies and various respiratory mechanics monitoring methods in COPD patients in recent years. It is expected to provide new ideas and references for the ventilation management of COPD patients who require mechanical ventilation in clinical practice.