Objective To investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α(RORA)in the proliferation and progression of colorectal cancer(CRC)cells.Methods The expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR,FISH,and IHC.Cell proliferation capability was detected through EdU and CFSE assay,cell apoptosis by flow cytometry assay,and cell migration and invasion abilities by cell scratch and Transwell invasion assays,respectively.The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay,cell function rescue test,RT-PCR,and Western blot assay.Finally,bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation,invasion,and progression of CRC via regulating RORA.Results miR-18a-5p exhibited a high expression in CRC tissues and cells(P<0.05)and promoted the proliferation,migration,and invasion of CRC cells(P<0.05).In addition,RORA served as the target gene of miR-18a-5p,and its overexpression effectively reduced the promoting function of miR-18a-5p in the malignant biological phenotype of CRC cells(P<0.05).The expression of RORA in CRC tissues showed a significantly positively correlation with the infiltration of CD8+T cells and the expression of its surface marker protein CD8A.Conclusion The targeted regulation of RORA by miR-18a-5p promotes the proliferation and progression of CRC.The miR-18a-5p/RORA regulatory pathway possibly contributes to the immune microenvironment of CRC,which can be a potential therapeutic target for CRC.

Objective: To explore the characteristics, patterns of multimorbidity and the impact on quality of life and the prognosis of middle-aged and elderly patients with chronic obstructive pulmonary disease (COPD). Methods: This is a cross-sectional study. From January 2012 to December 2021, 939 middle-aged and elderly COPD patients hospitalized in Beijing Hospital were selected by the convenient sampling method. The basic data of patients and the date of 16 common chronic diseases were collected. Patterns of multimorbidity were depicted by cluster analysis. Generalized linear regression model and logistic regression were used to evaluate the multimorbidity patterns and their prognosis. Results: At least one multimorbidity existed among 93.40% of COPD patients, and the median number of multimorbidity was 3. The top five multimorbidity among the patients were hypertension (57.93%, 544/939), coronary heart disease (33.76%,317/939), heart failure (31.95%,300/939), hyperlipidemia (31.63%,297/939) and arrhythmia (27.37%,257/939). Four multimorbidity patterns were identified, cardiometabolic and metabolic multimorbidity, kidney disease multimorbidity, respiratory-digestive-tumor multimorbidity and other multimorbidity. Cardiometabolic and metabolic multimorbidity was most common (590/939, 62.83%). Compared with non-cardiometabolic and metabolic multimorbidity, the incharge ADL score of patients with this multimorbidity decreased by 7 points (95%CI:-11.22- -3.34), Correspondingly, patients with kidney disease multimorbidity decreased by 14 points (95%CI:-24.12- -3.30) on the incharge score. The presence or absence of kidney disease multimorbidity had the greatest impact on discharge score, which was reduced by 12 points in comparison with patients without this multimorbidity (95%CI:-22.43- -2.40). ICU admission is mostly affected by the presence of cardiometabolic and metabolic multimorbidity (OR=2.44, 95%CI: 1.51-3.92) and kidney disease multimorbidity (OR=2.58, 95%CI: 1.01-6.60). The risk of death is the highest for cardiometabolic and metabolic multimorbidity (OR=2.24, 95%CI: 1.19-4.21). Conclusion: Multimorbidity is common in COPD patients. The most common pattern is cardiometabolic and metabolic multimorbidity. Cardiometabolic and metabolic multimorbidity and kidney disease multimorbidity significantly affect the quality of life and often associate with a poor prognosis.
Aged ; Middle Aged ; Humans ; Multimorbidity ; Inpatients ; Prevalence ; Cross-Sectional Studies ; Quality of Life ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Chronic Disease

Objectives: To investigate the clinical characteristics and prognoses of patients with anaplastic thyroid carcinoma(ATC), and to explore the value of multi-modality treatment in improving overall survival(OS) of ATC patients. Methods: Medical records including clinicopathological data of patients diagnosed with ATC at Cancer Hospital, Chinese Academy of Medical Sciences between 2001 and 2020 were retrospectively analyzed. The cohort were divided into surgery-only and multi-modality subgroups, and the latter included patients treated with surgery plus radiotherapy and/or medical therapy(including chemotherapy, target therapy and immunotherapy). Univariate survival analysis was conducted through Kaplan-Meier method, and multivariate survival analysis was performed using Cox proportional hazard model. Results: A total of 47 patients were included in the study, including 24 males and 23 females, with a median age of 63 years. After a median follow-up duration of 3.37 months, 42 patients died due to tumor recurrence or progression. The median OS of the cohort was 4.33 months. Univariate survival analysis demonstrated that symptoms of recurrent laryngeal nerve(RLN) involvement, distant metastasis, leukocyte elevation, and treatment modality were significantly associated with OS (P values all<0.05). Multivariate analysis showed that symptoms of RLN involvement(HR=2.49, 95%CI: 1.16-5.32, P=0.019), distant metastasis(HR=2.33, 95%CI: 1.06-5.16, P=0.036), and leukocyte elevation(HR=2.50, 95%CI: 1.16-5.40, P=0.020) were all independent risk factors for OS, while multi-modality therapy significantly prolonged OS compared with surgery alone(HR=0.22, 95%CI: 0.10-0.47, P<0.001). Conclusions: Among ATC patients, absence of symptoms of RLN invasion, normal leukocyte level and absence of distant metastasis at initial diagnosis are all independent protective factors for OS and multi-modality treatment can help to improve the prognosis.
Female ; Male ; Humans ; Middle Aged ; Retrospective Studies ; Thyroid Carcinoma, Anaplastic/therapy* ; Neoplasm Recurrence, Local ; Prognosis ; Thyroid Neoplasms/therapy*

Aim To observe the effect of epimedium on the proliferation and stem cell-like character expression of breast cancer cells, and investigate the relationship between the inhibition of stem cell-like character and miR-148a by epimedium, and its molecular mechanism. Methods After treatment with different concentrations of epimedium, cell viability and population dependence were detected by MTT assay and colony formation assay; the breast cancer stem cell-derived mammosphere formation was examined by Mammosphere assay; the expression levels of CD44,ALDH-1, Oct4,BMIl and EpCAM were detected by qPCR; the protein expression levels of EpCAM, SOX4, ZO-1, E-cadherin and vimentin were detected by Western blot; the protein localization of EpCAM was observed by im-munofluorescence assay; the effect of epimedium on migration was detected by wound healing assay. The miR-148a mimic was transfected into MDA-MB-231 cells, and the effects of epimedium on stem-like character expression of transfected MDA-MB-231 cells were observed. Results Epimedium significantly inhibited the proliferation and population dependence of MDA-MB-231 cells (P < 0.05 ), and reduced the breast cancer stem cell-derived mammosphere formation; compared with control group, epimedium significantly decreased mRNA levels of CD44, ALDH-1, Oct4, BMI1 and EpCAM (P <0.05) ,decreased protein contents of EpCAM, SOX4 and Vimentin (P < 0.05 ), up-regulated the protein expression of ZO-1 and e-cadherin ( P <0.05) ,and decreased the migration ability of MDA-MB-231 cells (P < 0.05). Epimedium up-regulated the expression of miR-148a in MDA-MB-231 cells (P <0.01). YYH + miR-148a mimic group significantly inhibited stem-like character expression and EMT process of breast cancer MDA-MB-231 cells compared with control group (P <0.05). Conclusions Epimedium can inhibit the proliferation of MDA-MB-231 cells, which may be related to the up-regulation of miR-148a, decrease of stem-like character expression of breast cancer cells,and inhibition of EMT.

Humans ; Pulmonary Disease, Chronic Obstructive ; Smoke/adverse effects* ; Tobacco ; Tobacco Smoke Pollution

Objective:To evaluate the relationship between preoperative widespread pain and chronic post-surgical pain (CPSP) following total knee arthroplasty (TKA) in the patients with knee osteoarthritis.Methods:Two hundred American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients with knee osteoarthritis, aged 40-70 yr, undergoing elective the first unilateral primary TKA under general anesthesia, were enrolled.The widespread pain index, visual analogue scale score, Hospital Anxiety and Depression Scale and Central Sensitization Inventory scores were recorded at 1 day before surgery.The patients were divided into CPSP-positive group and CPSP-negative group according to visual analogue scale score at 6 months after surgery.Risk factors for CPSP were analyzed by logistic regression.Results:The results of logistic regression analysis showed that increased preoperative widespread pain index score, Central Sensitization Inventory score and Hospital Anxiety and Depression Scale score and female were risk factors for CPSP after TKA.Conclusions:Preoperative widespread pain is a risk factor for CPSP following TKA in the patients with knee osteoarthritis.

The incidence of thyroid cancer continues to increase, among which differentiated thyroid cancer occupies the main position. Development of molecular biology has facilitated early diagnosis and precise treatment of thyroid carcinoma, and hopefully provided potential options for certain subtypes with poor prognosis, such as radioactive iodine-refractory differentiated thyroid carcinoma. This review summarizes the gene variants of high frequency and the mechanism of such gene variants, application of molecular biological detection in clinical diagnosis, as well as the correlation of specific gene variants with clinicopathological characteristics and prognosis for differentiated thyroid carcinoma.

Protein drugs play an extremely important role in the prevention and treatment of diseases. But the properties of macromolecules hinder their effects on intracellular targets. Among the existing delivery strategies, penetrating peptides are more suitable for clinical research and treatment, and have gradually become the most important tool to deliver protein drugs. Therefore, the development of safe and effective penetrating peptide delivery vehicles is of great significance to the basic research and clinical application of biomedicine. In this paper, a self-releasing intracellular transporter LCA2 based on the enterotoxin A2 domain is designed. This carrier is composed of three parts: a linker, self-releasing enzyme sensitive sites (Cs), and the transmembrane domain LTA2. The fluorescent protein mCherry was used as the model protein to detect the properties of LCA2. The results of electrophoresis showed that the high-purity mCherryLCA2 fusion protein was obtained from the engineered bacteria containing pET24a(+)-ma2 recombinant plasmids, and mCherry could be effectively separated from LCA2 by low concentration trypsin. It was observed under a fluorescence microscope that LCA2 could transport mCherry into different types of cells. Flow cytometry has detected that the transport capacity of LCA2 has certain cellular differences. Confocal microscope fluorescence analysis and Western blotting results showed that the mCherry was transported to the endoplasmic reticulum by the LCA2 carrier, separated from LCA2 by cleavage of enzyme sensitive sites and released into the cell. The CCK-8 results showed that there was no significant change in cell viability within the dose range of 5-40 μg/ mL. These results demonstrate that LCA2 is a safe and effective self-releasing delivery vehicle, which can transport and release active proteins or protein drugs into cells.

Objective:To evaluate the effect of parecoxib sodium on phenotypic transformation of alveolar macrophages in a mouse model of ventilator-associated lung injury (VALI).Methods:Forty-five SPF healthy adult male C57BL/6J mice, weighing 22-30 g, aged 8-12 weeks, were divided into 3 groups ( n=15 each) using a random number table method: sham operation group (S group), VALI group (V group) and parecoxib sodium group (P group). Lipopolysaccharide 20 ng was intraperitoneally injected, and 2 h later the animals were mechanically ventilated (tidal volume 30 ml/kg, respiratory rate 70 breaths/min, inspiratory/expiratory ratio 1∶2, fraction of inspired oxygen 21%, positive end-expiratory pressure 0) for 4 h to establish the model of VALI.Parecoxib sodium 30 mg/kg was intravenously injected at 1 h prior to mechanical ventilation in group P. The mice were sacrificed at 4 h of ventilation, the right lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of interleukin-6 (IL-6), IL-10 and tumor necrosis factor-alpha (TNF-α) concentrations (by enzyme-linked immunosorbent assay), expression of inducible nitric oxide synthase (iNOS) and arginase-1(Arg-1) in BALF and expression of phosphorylated Janus kinase 2 (p-JAK2) and phosphorylated signal transduction and transcription activator 3 (p-STAT-3) (by Western blot). The left lung was removed for determination of the wet/dry weight ratio (W/D ratio) and for examination of the pathological changes which were scored. Results:Compared with group S, the lung injury score, W/D ratio, concentrations of IL-6, IL-10 and TNF-α in BALF, and expression of iNOS, Arg-1, p-JAK2 and p-STAT-3 were significantly increased in V and P groups ( P<0.05). Compared with group V, the concentration of IL-10 in BALF and expression of Arg-1, p-JAK2 and p-STAT-3 were significantly increased, and the lung injury score, W/D ratio, concentrations of IL-6 and TNF-α in BALF and expression of iNOS were decreased in group P ( P<0.05). Conclusion:Parecoxib sodium promotes phenotypic transformation of alveolar macrophages from M1 subtype to M2 subtype and inhibits inflammatory responses, thus alleviating VALI, which may be related to activating JAK2/STAT-3 signaling pathway in mice.

Objective To evaluate the lung protective ventilation strategy on immune function in patients undergoing radical resection of lung cancer.Methods Sixty patients undergoing thoracoscopic radical resection of lung cancer, 47 males and 13 females, aged 35-64 years, BMI 18-29 kg/m2, falling into ASA physical statusⅠ orⅡ, were randomly divided into 2 groups with 30 cases in each:conventional mechanical ventilation (group C), protective mechanical ventilation group (group P).Volume-controlled ventilation was performed in the 2 groups.Protective mechanical ventilation mode was setted up as follows:tidal volume (VT) 8 ml/kg and respiratory rate (RR) 12-14 breaths/min during two-lung ventilation (TLV) ;VT 6 ml/kg, PEEP 5 cm H2O and RR 14-16 breaths/min during one-lung ventilation (OLV).Before induction of anesthesia (T0), at the end of surgery (T1), 24 hafter surgery (T2), 72 hafter surgery (T3), blood samples were taken from the central venous for determination of peripheral T lymphocyte subsets CD3+, CD4+, CD8+ and NK cell.The CD4+/CD8+ratio was also calculated.Results Compared with T0, the percentage of CD3+, CD4+, NK cell and the CD4+/CD8+ratio was significantly decreased at T1 and T2 in both groups (P<0.05).Compared with group P, the percentage of CD3+, CD4+, NK cell and the CD4+/CD8+ratio was significantly lower in the group C at T1 and T2 (P<0.05).Compared with T0, there was no significant difference at T3 with respect of the percentage of CD3+, CD4+, NK cell and the CD4+/CD8+ratio in the group P while those parameters still lower at T3 in the group C (P<0.05).Conclusion Perioperative use of lung protective ventilation strategy could not only alleviate the immune suppression but also make the immune function recover faster in patients undergoing thoracoscopic elective radical resection of lung cancer.