corona virus disease 2019 (COVID-19), which emerged at the end of 2019, is caused by infection with the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Due to the high mutability of SARS-COV-2, a variety of different types of mutant strains have emerged around the world, making the COVID-19 epidemic continues to spread around the world, posing a great threat and severe challenge to the global public health system. In November 2021, the Omicron (B.1.1.529)variant found in Botswana, southern Africa, is rapidly spreading globally with super infectivity, and has immediately attracted great attention worldwide because of its strong infectivity and immune evasion ability. In this paper, the latest research progresses on pathogenic characteristics, molecular mechanisms of immune evasion, vaccine tolerance and antibody tolerance of Omicron variant are briefly reviewed.

Objective To explore the differences in the intestinal flora between the glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) rat model and its effect on the modeling results of GA-ONFH. Methods Forty SD rats were randomly divided into four groups (n=10 for each group): control group, antibiotic (ABX) group, GA-ONFH model group, and ABX+GA-ONFH group. The ABX group and ABX+GA-ONFH group were continuously treated with an antibiotic solution to elute intestinal microorganisms for one week. One week later, the GA-ONFH model group and ABX+GA-ONFH group were intraperitoneally injected with lipopolysaccharide and dexamethasone to create an early GA-ONFH model; while the control group and ABX group received an equal volume of normal saline for six weeks. After six weeks, to evaluate correlation between intestinal flora and GA-ONFH modeling, the following experiments were conducted and analyzed from intestinal contents and femur samples: 1) the composition and abundance of fecal flora based on 16S rDNA amplicon sequencing technology; 2) Micro-CT and HE staining to observe the modeling results of early GA-ONFH. Results Compared with control group, the abundance of intestinal flora in GA-ONFH model group changed, and the abundance of Bacteroidetes was significantly down-regulated and Firmicutes was significantly up-regulated, with statistical significance (P<0.05); at the family level, the abundance of Prevotellaceae, Clostridia-UCG-014, Peptococcaceae, Rikenellaceae, and Christensenellaceae were significantly down-regulated, the abundance of Staphylococcaceae was significantly up-regulated, and the differences were statistically significant (P<0.05); at the genus level, the abundance of Alistipes, UCG-005, Clostridia_UCG-014, Alloprevotella, and Prevotellaceae_UCG-001 were significantly down-regulated, the abundance of Staphylococcus and Frisingicoccus were significantly up-regulated, with statistical significance (P<0.05).Micro-CT tomography showed subchondral trabecular sclerosis in both the GA-ONFH model group and ABX+GA-ONFH group after modeling. HE staining showed that trabecular bone fracture occurred earlier in the ABX+GA-ONFH group than in the GA-ONFH model group. After the gut microbial abundance was removed, the rat GA-ONFH modeling effect was more significant. Conclusion The intestinal flora of GA-ONFH model rats changed, and the change of intestinal flora may affect the occurrence of early GA-ONFH.

Objective To explore the correlation between smoking status and the risk of papillary thyroid carcinoma(PTC) in patients undergoing surgical treatment for thyroid nodules. Methods A retrospective analysis was conducted with the clinical data of 5938 patients (5156 cases with PTC and 782 cases with benign nodules) who underwent surgical resection of thyroid nodules in the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020, and with complete postoperative pathological results. The general information, serum thyroid hormone (TSH) level, thyroid autoantibody level, and the clinical and pathological characteristics of patients with different smoking status were compared between the two groups. The correlation between smoking status and the risk of PTC in patients of different genders and overall population were analyzed using binary logistic regression analysis. Results There no significant difference in percentage of smokers between PTC group and benign nodule group (P=0.104). The PTC group had a significantly lower proportion of smokers than the benign nodule group for males (P<0.05) rather than for females (P>0.05). For all patients, smokers had a lower proportion of PTC than non-smokers(OR=0.735, 95%CI 0.564-0.959) after adjustment for confounders. In the gender subgroup analysis, a lower risk of PTC was found in smokers than in non-smokers among men (OR=0.635, 95%CI 0.449-0.896), while no association was observed among women(OR=0.910, 95%CI 0.417-1.986) after adjustment for confounders. Conclusion Smoking in males may be associated with a reduced risk of developing PTC in patients undergoing surgical treatment for thyroid nodules.

Objective To investigate the risk factors of lymph node metastasis in papillary thyroid carcinoma (PTC)patients who had thyroid nodule operation. Methods The clinical data of 4742 patients, who had surgical treatment for thyroid nodule from January 2016 to December 2020 in the First Medical Center of Chinese PLA General Hospital, were collected for retrospective study. The pathologic specimens of thyroid and lymph nodes of all the patients were retained during surgery. The patients were divided into metastasis group (n=2407) and non-metastasis group (n=2335) according to lymph node metastasis. The differences of age, sex, body mass index, thyroid stimulating hormone (TSH) value, tumor diameter, capsule invasion, and range of glandular lobe involvement were analyzed between the two groups. The independent risk factors for lymph node metastasis of papillary thyroid carcinoma were evaluated by logistic regression, and multivariate regression analysis were performed based on tumor diameter dividing into subgroups of small and non-small cancers. Results In 4742 patients with PTC, the incidence of cervical lymph node metastasis was 50.8% (2407 cases). Multivariate analysis showed that male, age <45 years, increased tumor diameter, external thyroid extension (ETE), and multiple tumors were independent risk factors for cervical lymph node metastasis(P<0.001). BMI (P=0.369), TSH level (P=0.246) and Hashimoto thyroiditis were not associated risk factors. Subgroup analysis showed that unilateral multiple foci was an independent risk factor for lymph node metastasis in non-microcarcinomas (OR=1.67, 95%CI 1.20-2.31, P=0.002), and ETE in microcarcinomas was also a risk factor for lymph node metastasis (OR=1.58, 95%CI 1.27-1.96, P<0.001). Conclusion Male, <45 years old, tumor size ≥9.5 mm, ETE and multiple tumors are independent risk factors for cervical lymph node metastasis in PTC patients.

Objective To investigate the regulatory effect and molecular mechanism of circAPLP2 on invasion and metastasis of colorectal cancer cell SW480. Methods The online database Starbase was used to predict the binding sites of circAPLP2 and miR-497-5p, and TargetScan was used to predict the binding sites of miR-497-5p and FGFR1. The relative expression levels of circAPLP2 and miR-497-5p in LoVo, DLD1, SW480, SW620, Caco-2 and HCoEpiC cells were detected by qRT-PCR, and the relative expression level of FGFR1 protein was detected by Western blotting. SW480 cells were taken and set up as follows:(1) siNC group (transfected with siControl) and sicircAPLP2 group (transfected with sicircAPLP2), the expressions of circAPLP2, miR-497-5p, FGFR1 mRNA were detected by qRT-PCR, and the expression of FGFR1 protein was detected by Western blotting.(2) Vector group (transfected with empty plasmid) and circAPLP2 group (transfected with circAPLP2 overexpression plasmid), the expressions of miR-497-5p and FGFR1 mRNA were detected by qRT-PCR, and the expression of FGFR1 protein was detected by Western blotting. (3) siNC group (transfected with siControl), sicircAPLP2 group (transfected with sicircAPLP2) and sicircAPLP2+miR-497-5p inhibitor group (transfected with sicircAPLP2 and miR-497-5p inhibitor), the cell invasion was detected by Transwell, the cell migration was detected by scratch test, and the expressions of EMT marker proteins (E-cadherin, Twist1, N-cadherin and Vimentin) were detected by Western blotting. (4) NC miRNA group (transfected with NC-miRNA) and miR-497-5p mimics group (transfected with miR-497-5p mimics), or NC-inhibitor group (transfected with NC-inhibitor) and miR-497-5p inhibitor group (transfected with miR-497-5p inhibitor), the expression of FGFR1 was detected by qRT-PCR and Western blotting.(5) pcDNA-Control group (transfected with pcDNA-Control) and pcDNA-FGFR1 group (transfected with pcDNA-FGFR1), the expression of FGFR1 protein was detected by Western blotting. (6) NC-miRNA group (transfected with negative control), miR-497-5p mimics group (transfected with miR-497-5p mimics) and miR-497-5p mimics+pcDNA-FGFR1 group (co transfected with miR-497-5p mimics and pcDNA-FGFR1), the cell invasion, migration and the expression of FGFR1 and EMT marker proteins(E-cadherin, Twist1, N-cadherin, Vimentin) were detected by Transwell, scratch test or Western blotting. The circAPLP2-WT or circAPLP2-MT report plasmid was co-transfected with NC-miRNA or miR-497-5p mimics respectively for 48 h in SW480 cells, and the FGFR1-WT or FGFR1-MT report plasmid was co-transfected with miR-497-5p mimics and circAPLP2 respectively for 48 h in SW480 cells, and the luciferase activity was detected by the luciferase reporter gene detection system. Results The analysis results by Starbase and TargetScan showed that binding sites existed between circAPLP2 and miR-497-5p, and between miR-497-5p and FGFR1. Compared with human colon epithelial cell HCoEpiC, the relative expression level of circAPLP2 in colorectal cancer cells LoVo, DLD1, SW480, SW620 and Caco-2 increased significantly, while of miR-497-5p significantly decreased, and the relative expression level of FGFR1 protein significantly increased (P<0.05). After knocking down the expression of circAPLP2, compared with siCN group, the number of invasive cells in sicircAPLP2 group decreased (P<0.001), and the cell healing rate of scratches decreased (P<0.001), the expression of E-cadherin protein increased, and the protein expressions of Twist1, N-cadherin and Vimentin decreased (P<0.05). The results of dual luciferase reporter assay showed that miR-497-5p mimics decreased circAPLP2-MT luciferase activity significantly (P<0.001); MiR-497-5p inhibitor reverses the inhibitory effect of sicircAPLP2 on EMT, migration and invasion of colorectal cancer cells, as the number of invasive cells increased (P<0.001), the scratch healing rate increased (P<0.01), the expression of E-cadherin protein decreased, and the expression of Twist1, N-cadherin, and Vimentin protein increased (P<0.05). Dual luciferase reporter assay results showed that miR-497-5p mimics significantly reduced FGFR1-MT luciferase activity (P<0.001). Over-expression of FGFR1 reversed the inhibition of miR-497-5p overexpression on colorectal cancer cell migration and invasion, manifested as increased number of invasive cells (P<0.001), increased scratch healing rate (P<0.01), decreased expression of E-cadherin, increased expressions of N-cadherin, Twist1 and Vimentin (P<0.05). Conclusion The expression level of circAPLP2 increases in colorectal cancer cells, it may promote the expression of FGFR1 through competitive combination with miR-497-5p, thus promoting EMT, invasion and migration of colorectal cancer cells.

The perioperative brain injury is an important factor leading to poor clinical treatment effect and poor prognosis of critically ill patients undergoing cardiac surgery. In order to reduce the incidence of brain injury complications during perioperative period of cardiac disease, decrease the adverse consequence of brain injury, improve the neurological rehabilitation of patients after cardiac surgery, and enhance the quality of life and obtain the best prognosis of patients. Cardiac Intensive Care Professional Committee of Chinese Medical Doctor Association, Critical Care Medicine Professional Committee of Chinese Medical Education Association, Cerebral Protection in Cardiac Intensive Care Group of Neural Regeneration and Repair Committee of Chinese Research Hospital Association, and Liaoning Province Internet Intelligent Combination of Medical Care Professional Committee write the consensus. It aims to help clinicians improve the level of diagnosis and treatment of brain injury during perioperative period of cardiac critical care patients. The consensus include the characteristics and mechanisms of Chinese and Western medicine, monitoring methods, Chinese and Western medicine intervention and treatment of perioperative brain injury in adult cardiac surgery, thus providing apply reference for clinical work.

Objective To explore the consistency of ultrasonography and histopathology in diagnosis of Hashimoto thyroiditis. Methods The clinical data of 6238 patients, who underwent surgical treatment for thyroid nodules in the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020, were collected and retrospectively analyzed. The preoperative thyroid function and ultrasound examination data of the included patients were complete, and the postoperative pathological results were clear. The effectiveness of ultrasound imaging in diagnosis of Hashimoto thyroiditis was analyzed, and the consistency between ultrasound and pathological diagnosis was evaluated by use of Cohen's kappa coefficient (κ). According to the preoperative thyroid stimulating hormone (TSH) level, the patients were divided into TSH elevated group (n=329), TSH normal group (n=5662) and TSH decreased group (n=247). The diagnostic efficacy of ultrasound examination under different preoperative thyroid function states and its consistency with pathological diagnosis were discussed. Results (1) Among the 6238 patients, preoperative ultrasound examination revealed 1549 cases of Hashimoto thyroiditis, and postoperative pathological diagnosis revealed 1182 cases of Hashimoto thyroiditis; Only 687 patients (58.1%) had positive ultrasound and pathological diagnoses. Among the confirmed patients, 88.7% were women (1048/1182) and 11.3% were men (134/1182); The three typical ultrasound manifestations in women, including reduced parenchymal echo (17.9% vs. 11.8%), grid like changes (7.5% vs. 4.7%), increased blood flow (14.5%vs. 8.3%, P<0.001), as well as the positive rate of ultrasound diagnosis (27.8% vs. 17.1%, P<0.001) and pathological diagnosis (23.3%vs. 7.7%, P<0.001), were significantly higher than those in men. (2) Consistency analysis showed that the consistency between ultrasound diagnosis and pathological diagnosis was general (κ=0.367). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of ultrasound diagnosis were 58.1%, 83.0%, 44.4%, 89.4% and 78.2%, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of single imaging features (reduced parenchymal echo, grid like changes and increased) were 33.2%, 22.0%, 28.8%, 87.8%, 96.9%, 91.0%, 38.8%, 62.4%, 42.7% and 84.9%, 84.2%, 84.5%, respectively.The accuracy was 77.4%, 82.7% and 79.2%, respectively. Receiver operating characteristic (ROC) curve analysis showed that the predictive value of single imaging feature or the combination of two imaging features was poor in diagnosis. Among them, reduced parenchymal echo and reduced parenchymal echo combined with grid like changes were slightly better in diagnosis. (3) The positive rates of ultrasound and pathological diagnosis were higher in preoperative TSH elevated group and TSH decreased group (57.9% and 52.2% respectively in TSH elevated group; and 33.7% and 15.5% respectively in TSH decreased group, while TSH normal group was lower (22.9% and 17.7%, respectively). In addition, the consistency between ultrasound and pathological diagnosis in elevated TSH group was relatively the best, close to moderate (κ=0.399). Conclusions Both ultrasound diagnosis and single imaging features have good specificity and poor sensitivity in the diagnosis of Hashimoto thyroiditis. The consistency between ultrasound diagnosis and pathological diagnosis is general, and the consistency is slightly enhanced when combined with preoperative TSH elevation, but it can only be used as a reference. For female patients having thyroid dysfunction; the significance of combined ultrasound diagnosis will be greater. Ultrasonography is a convenient and quick supportive diagnosis of Hashimoto 's thyroiditis.

Acute respiratory distress syndrome (ARDS) refers to acute diffuse lung injury and subsequent acute respiratory failure caused by various intrapulmonary and extrapulmonary pathogenic factors, with respiratory distress and refractory hypoxemia as clinical features. At present, the "standardized" mechanical ventilation for ARDS patients is a lung protective ventilation strategy with low tidal volume and high positive end-expiratory pressure. However, the results are often unsatisfactory, and most related clinical studies have ended up unsuccessfully. Because of the high heterogeneity of ARDS, accurate classification and individualized treatment are very important. In this paper, we reviewed the phenotypes of ARDS from the perspectives of etiology, onset time, disease severity, inflammation level, imaging characteristics pathology, etc., and preliminarily explained the ARDS phenotype associated with COVID-19, and summarized the individualized treatment strategies for ARDS with different phenotypes, hoping to provide evidence for the individualized and precise treatment of ARDS.

Objective To preliminarily observe the pyroptosis of splenic dendritic cells (DC) in septic mice and its correlation with the levels of inflammatory factors and DC immune function. Methods Seventy BALB/c mice were randomly divided into sham group (n=20), sepsis model group (CLP group, n=30) and caspase (CASP)-1 inhibit group (CLP+YVAD group, n=20). The CLP group and CLP+YVAD group were then divided into CLP 12 h group, CLP 24 h group, CLP 48 h group and CLP 72 h group, and CLP+YVAD 24 h group and CLP+YVAD 72 h group at different time points after operation. Orbital blood was collected from all mice at a predetermined time after operation, and the mice were sacrificed and spleen tissues were extracted. The pyroptosis rate of DC and the expression levels of DC surface markers (CD80, CD86, MHC-Ⅱ) were determined by flow cytometry.Activation of CASP-1 in mouse spleen DC was observed using confocal laser microscope. Western blotting was used to determine the expression of CASP-1 in DC. ELISA was performed to measure the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-12, IL-1β, and IL-6 in serum. Observe the death of mice after CLP operation. BALB/c mouse T cells were extracted and co-cultured with the mouse spleen DC of each group, the T cell proliferation rate was measured by flow cytometry, and the concentrations of interferon (IFN)-γ, IL-4 and IL-10 in the co-cultured supernatants were detected by ELISA. Results The pyroptosis rate of DC was increased 12 h after CLP compared to sham group (P<0.05), peaked at 24 h (P<0.01), and then progressively declined, but remained higher than sham group at 72 h after CLP (P<0.01). Confocal laser microscopy revealed that the activation of DC CASP-1 in spleen of mice after CLP was obvious. Western blotting showed the expression of CASP-1 in the early stage of sepsis (12 h and 24 h) was significantly higher than that in sham group (P<0.01). After administration of CASP-1 specific inhibitor Ac-YVAD-cmk, the DC pyroptosis rate at CLP+YVAD 24 h group was lower than that in CLP 24 h group (P<0.01). The expression levels of DC surface markers CD80 and MHC-Ⅱ at CLP+YVAD 72 h group were up-regulated compared with CLP 72 h group (P<0.01), and the survival rate of mice at 7 d after operation was improved (P<0.01). The results of ELISA showed that the concentrations of serum TNF-α, IL-12, IL-1β and IL-6 of CLP mice in the early stage (24 h) and late stage (72 h) of sepsis were significantly higher than those in sham group (P<0.01), while the serum concentrations of the above factors in CLP+YVAD group decreased significantly(P<0.01). In the co-culture experiment, compared with DC-CLP 24 h group, the T cell proliferation rate of DC-CLP+YVAD group significantly increased (P<0.01), the level of IFN-γ decrease in co-cultured supernatants, and the levels of IL-4 and IL-10 increased(P<0.01). Conclusions Pyroptosis of DC appears to be activated at the early stage upon septic challenge, might be an important pathophysiological mechanism with regard to the extensive release of inflammatory cytokines as well as immune suppression of DC, which is associated with poor prognosis of sepsis.

Cachexia is a serious chronic wasting syndrome, which is a common complication of cancer, end-stage heart failure and other diseases. The abnormal inflammatory response in the process of cachexia plays an important role in the loss of muscle and fat, the proliferation and metastasis of tumors. In recent years, it has been found that microRNA and long non-coding RNA (lncRNA) carried in exosomes can mediate cell-to-cell communication, activate related signaling pathway to secrete various inflammatory factors. It mediates the inflammatory response of cachexia, affects the formation of local and distal inflammatory microenvironment, promotes tumor cell proliferation, metastasis and inhibits its apoptosis, thereby accelerating the progression of cachexia. This review mainly summarizes the relationship between exosome and cachexia inflammation response, the harm of cachexia inflammation response and the mechanism of action, and provides new ideas for preventing it and slowing down the cachexia progress.