Latest ArticlesObjective To investigate the effects of inhibiting KDM2A gene on the proliferation, invasion and migration of liver cancer cells and its possible regulatory mechanism. Methods Forty pairs of HCC tissues and their adjacent normal counterparts were collected from 2014 to 2017 in Tongji Hospital, Tongji Medical College Affiliated to Huazhong University of Science and Technology. Human liver cancer cell lines HepG2, Huh7, HCCLM3, MHCC-97H and normal liver cells LO2 were cultured in vitro. The mRNA and protein expression levels of KDM2A in HCC tissues and cells were detected by qRT-PCR and Western blotting. Huh7 cells were taken and set up as follows: (1) si-NC group (transfected with si-NC) and si-KDM2A group (transfected with si-KDM2A); (2) mimic-NC group (transfected with mimic-NC), miRNA-29a-3p mimic group (transfected with miRNA-29a-3p mimic), inhibitor-NC group (transfected with inhibitor-NC) and miRNA-29a-3p inhibitor group (transfected with miRNA-29a-3p inhibitor). The mRNA and protein expression levels of KDM2A were detected by qRT-PCR and Western blotting. The invasion and migration of cells were detected by Transwell, the proliferation of cells was detected by CCK-8 methods. The online databases TargetScan, miRDIP, miRWalk, Starbase and miRDB were used to predict the binding sites of KDM2A and miR-29a-3p. The KDM2A 3'-UTR (WT) or KDM2A 3'-UTR (MUT) report plasmid was co-transfected with NC-miRNA or miR-29a-3p mimics respectively for 48 h in 293T cells, and the luciferase activity was detected by the luciferase reporter gene detection system. Results Compared with adjacent normal counterparts, the relative mRNA and protein expression levels of KDM2A in HCC tissues increased significantly (P<0.05). Compared with LO2, the relative mRNA and protein expression levels of KDM2A in HepG2, Huh7, HCCLM3 and MHCC-97H increased significantly (P<0.05). Compared with si-NC group, the proliferation, invasion and migration of Huh7 cells in si-KDM2A group decreased significantly (P<0.05 or P<0.01). The analysis results of TargetScan, miRDIP, miRWalk, Starbase and miRDB showed that there were binding sites between KDM2A and miR-29a-3p. The results of the dual luciferase reporter assay showed that miR-29a-3p mimic significantly reduced KDM2A-MUT luciferase activity (P<0.01). After overexpression of miRNA-29a-3p, the relative mRNA and protein expression levels of KDM2A were decreased (P<0.01), the proliferation, invasion and migration abilities were decreased (P<0.05) in Huh7 cells. After inhibiting the expression of miRNA-29a-3p, the relative mRNA and protein expression levels of KDM2A were increased (P<0.05), the proliferation, invasion and migration abilities were enhanced (P<0.05) in Huh7 cells. Conclusion Inhibiting the expression of KDM2A can reduce the proliferation and migration ability of Huh7 cells. miR-29a-3p may be the upstream regulator of KDM2A and participate in the occurrence and development of hepatocellular carcinoma.
Objective To report the clinical and imaging characteristics of a case with the clinical manifestation of multiple lung and liver nodules, diagnosed as IgG4-related hepatic inflammatory pseudotumor (HIPT) complicated by hepatic tissue-infection, and review the literature in order to facilitate clinical diagnosis and differential identification of IgG4-related HIPT. Methods A retrospective analysis was conducted on the medical records of a patient with IgG4-related disease (IgG4-RD) characterized by multiple lung and liver nodules. A literature review was performed by searching Chinese and English databases to summarize the clinical and imaging characteristics of IgG4-related HIPT and hepatic tissue infection. Results The case involved a 64-year-old female admitted to the Rheumatology and Immunology Department of the First Medical Center of Chinese PLA General Hospital due to "poor appetite and fatigue for over a year, and dry cough for four months". She presented with multiple nodules in the lungs and liver, without involvement of the eyelids, salivary glands, submandibular glands, or pancreas. Laboratory test results revealed elevated serum IgG4 levels at 14.1 g/L and C-reactive protein (CRP) at 82.1 mg/L. Pulmonary CT scans indicated multiple solid nodules in both lungs with clear boundaries. Abdominal contrast-enhanced MRI revealed a nodule in liver segment S7 with a pseudocapsule around it, clear boundaries, and uniform enhancement; another nodule in liver segment S5 with blurred boundaries and ring enhancement. The final diagnosis of the liver nodules was confirmed by pathological and metagenomic sequencing to be an IgG4-related HIPT in segment S7 and hepatic tissue infection in segment S5. After a full course of anti-infection and treatment with methylprednisolone and leflunomide, follow-up imaging showed near-complete resolution of the lung and liver nodules. Literatures were searched in China National Knowledge Infrastructure (CNKI), Wanfang, and PubMed databases (up to September 2023), and no case of IgG4-RD complicated with both liver involvement and infection was found. A total of 26 cases of IgG4-RD involving the liver have been reported so far, predominantly in males (92.3%), with an average age of 51 years. Most patients presented with abnormal liver function as the initial symptom, with normal blood inflammatory markers. Imaging typically shows a single nodule in 88.5% of cases, with clear boundaries and uniform enhancement, as well as ring enhancement. Concurrent involvement of the pancreas and biliary tract is common. Pathology is the gold standard for confirming the disease. Conclusions This case reports coexistence of IgG4-related HIPT and infection within multiple hepatic nodules. In the diagnosis and treatment of patients with IgG4-RD presenting with multiple hepatic nodules, if the imaging characteristics of the nodules are inconsistent, it is necessary to consider the possibility of the underlying disease coexisting with other conditions, which can be easily misdiagnosed. Actively obtaining pathological tissue is crucial for aiding in the definitive diagnosis.
Objective To explore the clinicopathological characteristics, prognosis and influencing factors of different pathological subtypes of gastric signet ring cell carcinoma (GSRC). Methods A retrospective analysis was performed on the clinical data of 232 patients with GSRC collected from January 2016 to December 2018 in Lanzhou University Second Hospital. According to the WHO classification criteria for GSRC, the patients were divided into pure gastric signet-ring cell carcinoma (pGSRC, n=36) and mixed gastric signet-ring cell carcinoma (mGSRC, n=196). The follow-up as of September 30, 2022, the survival analysis was done using Kaplan-Meier method, the univariate and multivariate Cox regression were performed to analyze the risk factors affecting the prognosis of GSRC patients. Results The median survival time of pGSRC and mGSRC patients was 41.0(6.0-70.0) months and 24.0(2.0-74.0) months, respectively. Kaplan-Meier analysis showed that combination with diabetes, anemia, tumor diameter, nerve invasion, lymphovascular invasion, T stage, N stage, GSRC pathological subtype, CA125 and tumor diameter could affect the overall survival (OS) of patients with GSRC after radical gastrectomy (P<0.05), but Her-2, whether adjuvant chemotherapy or not and others elements had no significant effect on OS of GSRC patients after radical gastrectomy (P>0.05). Univariate Cox regression analysis showed that the combination with diabetes (P=0.031), anemia (P=0.028), tumor diameter >5 cm (P=0.009), nerve invasion (P=0.002), lymphovascular invasion (P=0.002), mGSRC pathological type (P=0.039), T2-T4 stage (P=0.001), N1-N4 stage (P=0.004), pTNM stage Ⅲ (P=0.044), the number of lymph node metastasis >30 (P=0.044) and CA125 positive (P=0.009) were related to the prognosis of patients with GSRC after radical gastrectomy. Multivariate Cox regression analysis showed that mGSRC pathological type (P=0.035), T2-T4 stage (P=0.003), CA125 positive (P=0.010) were independent risk factors for poor prognosis of patients with GSRC after radical gastrectomy. Conclusion Compared with pGSRC, patients with mGSRC at diagnosis have higher pTNM stages, more aggressive, and shorter median survival time. mGSRC pathological type, T2-T4 stage, and CA125 positive were all independent factors affecting the prognosis of patients with GSRC.
Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease, and hip preservation surgery has high clinical value in the early stages of ONFH, especially for young and middle-aged patients. However, the repair of ONFH is heterogeneous, leading to inter-individual variations in the efficacy of hip preservation. Currently, the existing tissue-engineered scaffolds in the field of hip preservation are uncontrollable after implantation, making it difficult to achieve precise repair. Smart responsive materials have good biocompatibility and self-feedback capability. By combining them with therapeutic drugs to construct stimulus-responsive drug delivery systems, new possibilities are provided for the precise repair of ONFH. This paper reviews the research progress of smart responsive materials at home and abroad. Based on the response principles of various materials and the repair characteristics of ONFH, the application prospects of various smart responsive materials such as reactive oxygen species-responsive, fluid shear stress-responsive, and light/magnetic-responsive materials are discussed and prospected in the field of precise repair for ONFH, providing new ideas for the precise treatment of ONFH.
Objective To evaluate the perioperative anxiety state and analyze the influencing factors of burned patients. Methods A total of 110 burned patients undergoing selective surgery under general anesthesia were included in the Fourth Medical Center of Chinese PLA General Hospital from February to August 2022. All patients were evaluated with self-rating anxiety scale (SAS), visual analogue scale-anxiety (VAS-a), visual analogue scale-pain (VAS-p), mini-mental state examination (MMSE), and Ramsay sedation score 1-day before and after operation. The patients' parameters were recorded including mean arterial pressure (MAP) and heart rate (HR) at admission (T0), before anesthesia induction (T1), 2 min after intubation (T2), 15 min after surgery (T3), during surgery (T4), at surgery end (T5), and immediately after leaving the operating room (T6). The occurrence and the influencing factors of perioperative anxiety in burn patients were analyzed using the univariate and multivariate logistic regression. Results The incidence of preoperative and postoperative anxiety in burn patients was 29.1% and 22.3% respectively. Univariate logistic analysis showed that gender (P=0.002), burn time (P=0.046), burn area (P=0.005), burn site (P=0.035), and degree of preoperative pain (P=0.001) were related with preoperative anxiety status in burn patients; while burn time (P=0.030), burn area (P=0.001), burn site (P=0.016), degree of preoperative pain (P=0.021), and preoperative anxiety status (P<0.001) were related with postoperative anxiety state in burn patients. Multivariate logistic regression analysis showed that gender and degree of preoperative pain were the independent influencing factors of preoperative anxiety status in burn patients (P=0.002, 0.022), and preoperative anxiety status was the independent influencing factor of postoperative anxiety status in burn patients (P<0.001). Compared with the preoperative non-anxious patients (n=73), preoperative anxious patients (n=30) showed no significant difference in MAP at each time point (P>0.05), but HR was accelerated (P<0.05), and the dosage of sufentanil, remifentanil and propofol increased significantly during the operation (P<0.05). Conclusions The anxiety state of burn patients was significantly higher before operation than that after operation, and their consumption of anesthetic drugs during operation was higher, and there was no significant correlation with the type and number of operation. Gender, degree of preoperative pain and anxiety state were the independent influencing factors of perioperative anxiety state in burn patients. Early intervention against relevant factors will help patients recover quickly.
Objective To investigate risk factors for acute phase reaction (APR) induced by zoledronic acid (ZA) treatment in osteoporosis and its impact on treatment adherence and persistence. Methods A retrospective analysis was conducted using clinical data from 471 osteoporosis patients with a median age of 67 years, who received 5 mg ZA in the First Affiliated Hospital of Chongqing Medical University between January 2013 and January 2022. Patients were divided into two groups based on the occurrence of APR: APR group (n=79) and non-APR group (n=392). Univariate and multivariate logistic regression analyses were used to identify factors inducing APR. The treatment persistence of ZA was analyzed using Kaplan-Meier curves. In addition, treatment adherence was analyzed. Results The incidence of APR was 33.2% after the first ZA injection, and it gradually decreased with an increase in the number of infusions. The multivariate logistic regression analysis showed that the first infusion, no history of oral bisphosphonate use, and high blood phosphorus levels were independent risk factors for APR. Three-year treatment adherence and persistence in APR group were 53% and 44%, respectively, while in non-APR group, they were 52% and 42%, respectively. Kaplan-Meier analysis showed no statistically significant difference in the persistence of ZA between two groups (P>0.05). Conclusions APR is prone to occur during ZA treatment for osteoporosis, but it does not affect the adherence and persistence of ZA treatment. First use of ZA, no history of oral bisphosphonates, and high blood phosphorus levels are independent risk factors for APR.
Objective To investigate the influences and mechanism of X chromosome inactivation specific transcript (XIST) on the proliferation and extracellular matrix synthesis of nucleus pulposus cells in rats with intervertebral disc degeneration (IDD). Methods SD rat intervertebral disc nucleus pulposus cells were isolated and cultured in vitro, and then randomly divided cells into control group, model group, XIST knockdown group, empty plasmid group, and XIST knockdown+miR-132-3p knockdown group. Except for control group, the cells in other groups were induced by interleukin (IL)-1β to establish IDD models. After nucleus pulposus cells were grouped and treated, the expressions of XIST and miR-132-3p in the nucleus pulposus cells of rats were detected by qRT-PCR; the proliferation of intervertebral disc nucleus pulposus cells was detected by MTS method and EdU staining; ELISA was used to measure the levels of inflammatory factors IL-6 and IL-18 in the intervertebral disc nucleus pulposus cells; Immunoblotting was used to detect the expression of extracellular matrix labeled proteins Collagen Ⅱ and Aggrecan in rat nucleus pulposus cells. The targeted regulation of miR-132-3p by XIST in rat nucleus pulposus cells was detected by dual-luciferase reporter gene assay. IDD rat models were established by intramuscular injection of IL-1β and divided into sham operation group, model group, XIST knockdown group, no-load plasmid group, XIST knockdown+miR-132-3p knockdown group, with 12 rats in each group. After treatment in each group, the expressions of XIST and miR-132-3p in intervertebral disc tissues were detected by qRT-PCR; TUNEL staining was used to detect apoptosis of nucleus pulposus cells in intervertebral disc tissue of rats; the morphology of intervertebral disc cartilage was observed by saffron O staining; serum levels of inflammatory factors IL-6 and IL-18 were determined by ELISA; the expressions of Collagen Ⅱ and Aggrecan in intervertebral disc tissues were detected by Western blotting. Results Compared with control group (cells)/sham operation group (rats), XIST expression in intervertebral disc tissue and nucleus pulposus cells, apoptosis rate of intervertebral disc nucleus pulposus cells, levels of inflammatory factors IL-6 and IL-18 in intervertebral disc nucleus pulposus cells culture medium and serum were increased in model group (P<0.05), the activity and proliferation rate of nucleus pulposus cells and the expressions of miR-132-3p, Collagen Ⅱ and Aggrecan protein in nucleus pulposus cells and intervertebral disc tissues decreased (P<0.05); compared with model group, the apoptosis rate of nucleus pulposus cells, the levels of inflammatory factors IL-6 and IL-18 in intervertebral disc nucleus pulposus cells culture medium and serum, and the expression of XIST in nucleus pulposus cells and intervertebral disc tissues of rats in XIST knockdown group decreased (P<0.05), the activity and proliferation rate of nucleus pulposus cells and the expressions of miR-132-3p, Collagen Ⅱ and Aggrecan protein in nucleus pulposus cells and intervertebral disc tissues increased (P<0.05). Down-regulation of miR-132-3p attenuates the ameliorative effect of knockdown XIST on IL-1β-induced intervertebral disc injury and cartilage matrix loss. XIST was able to target and down-regulate the expression of miR-132-3p in rat nucleus pulposus cells. Conclusion Knockdown of XIST can inhibit inflammation by up-regulating miR-132-3p, thereby inhibiting the apoptosis of IDD nucleus pulposus cells and promoting their proliferation and extracellular matrix synthesis.
Objective To analyze the incidence and mortality of malignant tumors among the middle-aged and elderly population in Chengguan district of Lanzhou from 2011 to 2021, and to discuss the related risk factors. Methods Using the research data of REACTION in Lanzhou, an epidemiological survey was conducted through cluster sampling in three communities in Chengguan district of Lanzhou since April 2011. The target population was middle-aged and elderly residents over 40 years old. Two follow-up surveys were carried out in 2014-2016 and 2021 successively, and 6543 people with complete follow-up data were finally included. The incidence and mortality rates of malignant tumors were calculated, as well as their age standardized rates with reference to the age composition of Segi's world standard population. Multivariate Cox regression analysis was used to screen the risk factors affecting the incidence and mortality of malignant tumors. Results After an average follow-up of 10.6 years, 314 new cases of malignant tumors were found in middle-aged and elderly residents in Chengguan district of Lanzhou, with an incidence rate and age standardized incidence rate of 454.30/100 000 and 128.93/100 000, respectively. A total of 158 deaths were attributed to malignant tumors, with a mortality rate and age standardized rate of 228.41/100 000 and 607.9/100 000, respectively; The age standardized incidence rate and mortality rate of malignant tumors males were both higher than those females (P<0.05). During the follow-up period, the age standardized incidence rate of malignant tumors in the general population showed an significant upward trend (P<0.05), whereas the age standardized mortality rate gradually decreased after a brief increase (P<0.05). Lung cancer, colorectal cancer, gastric cancer, and liver cancer were the main types of malignant tumors ranking in the top five in terms of incidence and mortality by gender. Multivariate Cox regression results indicate that male, age ≥60 years old, college education level or above, smoking history, drinking history, having been hit by major stressful events, central obesity, hypertension, and coronary heart disease are risk factors for the onset or death of malignant tumors (HR>1). Married, with family size ≥4, frequent consumption of fresh fruit, frequent consumption of fresh vegetables, frequent consumption of grains and tubers are protective factors for the onset or death of malignant tumors (HR<1). Conclusion The incidence of malignant tumors among middle-aged and elderly people in Chengguan district of Lanzhou from 2011 to 2021 showed an increasing trend, while the overall mortality was decreasing. Our study indicates early cancer screening in elderly populations, maintaining a healthy lifestyle and strengthening the management of chronic diseases are crucial for the prevention and treatment of malignant tumors.
Objective To investigate the diagnostic value of CT radiomics features in pulmonary alveolar proteinosis (PAP). Methods The general data and clinical characteristics of 24 patients with PAP in the Chinese PLA General Hospital from November 2008 to August 2022 were retrospectively collected and analyzed. Another 53 patients with other diffuse lung diseases except for PAP during the same period served as control group. The differences in the 10 conventional CT signs (semantic features) and 107 radiomics features between the two groups were compared. All patients were randomly divided into the training group (n=53) and the validation group (n=24) at a ratio of 7:3. CT semantic feature model, radiomics model and combined model to diagnose PAP were constructed in training group, and the diagnostic efficacy of models was compared using the receiver operating characteristic (ROC) curve in validation group. Decision curve analysis (DCA) was used to assess the value of models for practical clinical application. Radscore was calculated for the model with the highest diagnostic efficacy. Results A total of 24 patients with pathologically confirmed PAP were enrolled, with a male to female ratio of 3:1 and an average age of (44.6±15.2) years. The main clinical symptoms of patients with PAP included shortness of breath, cough, sputum and chest tightness. Compared with control group, the incidence of pleural effusion in PAP group was significantly lower (P<0.05), while no significant differences were observed in other CT features (P>0.05). The areas under the curve (AUC) of the semantic feature model for diagnosing PAP in training and validation group were 0.590 and 0.594, respectively, and in validation group, the accuracy, sensitivity, and specificity for diagnosis of PAP were 0.188, 1.000, and 0.188, respectively. The AUCs of the radiomics model in training group and validation group were 0.845 and 0.867, respectively, and in validation group, the accuracy, sensitivity, and specificity were 0.641, 0.938, and 0.703, respectively. The AUCs of the combined model in training group and validation group were 0.850 and 0.883, respectively, and in validation group, the accuracy, sensitivity, and specificity were 0.688, 0.750, and 0.938, respectively. The AUCs of the radiomics model and the combined model were significantly greater than that of the semantic feature model, but there was no significant difference in the AUCs between the first two models. The decision curve analysis showed that both the radiomics model and the combined model had high application value for predicting PAP. Conclusion CT radiomics shows higher clinical value in the diagnosis of PAP compared with conventional CT features.
Objective To investigate the role and underlying mechanisms of miR-34a/SIRT1 in intensive care unit acquired weakness (ICU-AW). Methods (1) C2C12 mouse skeletal muscle cells were induced to differentiate into myotubes, and were divided into two groups: model group [ICU-AW group, treated with lipopolysaccharides (LPS) for 12 hours] and normal control group (treated with the same amount of sterile water for 12 hours). Western blotting was used to detect the protein expression level of Muscle ring finger 1 (MuRF-1), atrophy gene 1 (Atrogin-1) and Sirtuin-1 (SIRT1). RT-qPCR was used to assess the mRNA expression level of microRNA-34a (miR-34a), MuRF-1, Atrogin-1 and SIRT1, and light microscope was used to observe the growth and differentiation of C2C12 skeletal muscle cells in each group. (2) ICU-AW cells were further subdivided into control group (treated with siRNA transfection agent intervention), Scra siRNA group (treated with transfection agent and non-specific siRNA), miR-34a siRNA group (treated with transfection agent and specific siRNA intervention), vehicle group (treated with agonist solvent dimethyl sulfoxide) and SRT1720 group (treated with SIRT1 agonist SRT1720). Western blotting was used to detect the protein expression level of SIRT1, Atrogin-1 and MuRF-1 in each group. RT-qPCR was used to detect the miR-34a and the mRNA expression level of SIRT1, Atrogin-1 and MuRF-1 in each group. (3) In addition, another group of ICU-AW cells were divided into control group (treated with siRNA transfection), miR-34a siRNA group (treated with transfection agent and specific siRNA intervention), miR-34a siRNA+vehicle group (treated with transfection agent, specific siRNA and Dimethyl sulfoxide intervention) and miR-34a siRNA+EX-527 group (treated with transfection agent, specific siRNA and SIRT1 inhibitor EX-527). Western blotting was used to detect the protein expression level of Atrogin-1 and MuRF-1. RT-qPCR was used to assess the mRNA expression level of Atrogin-1 and MuRF-1. Results Myotube differentiation was observed on the 4th day. Compared with control group, myotube atrophy was obvious in ICU-AW group. RT-qPCR and Western blotting results revealed that, compared with normal control group, in ICU-AW group, the mRNA and protein expression levels of Atrogin-1 and MuRF-1 significantly increased (P<0.05), and the expression level of miR-34a significantly increased (P<0.05), while the mRNA and protein expression levels of SIRT1 significantly decreased (P<0.05). RT-qPCR results showed that, compared with control group (treated with siRNA transfection agent intervention) and Scra siRNA group, the expression of miR-34a and mRNA expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group significantly decreased (P<0.05), while the mRNA expression of SIRT1 significantly increased (P<0.05), meanwhile the protein expression of Atrogin-1 and MuRF-1 decreased significantly (P<0.01), and the protein expression of SIRT1 significantly increased (P<0.05). RT-qPCR results also showed that, compared with vehicle group, the mRNA expression of Atrogin-1 and MuRF-1 in SRT1720 group decreased significantly (P<0.05), while SIRT1 increased significantly (P<0.05). Western blotting results demonstrated that, compared with control group and Scra siRNA group, the protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA group decreased significantly (P<0.05), while SIRT1 increased significantly (P<0.05). RT-qPCR and Western blotting results indicated that, compared with miR-34a siRNA+vehicle group, the mRNA and protein expression of Atrogin-1 and MuRF-1 in miR-34a siRNA+EX-527 group increased significantly (P<0.05). Conclusion Overactivation of miR-34a in ICU-AW contributes to skeletal muscle atrophy by inhibiting the expression of SIRT1, which may play an important role in the pathogenesis of ICU-AW.