Objective To investigate the role of CYFIP2 gene in proliferation and migration of renal clear cell carcinoma(KIRC). Methods The TCGA database was used to analyze the expression of CYFIP2 gene in KIRC and the correlation between the expression and clinicopathological factors. The KIRC cell line 786-O was transfected with siRNA-CYFIP2 to knockdown the CYFIP2 gene, and the CYFIP2 gene stable overexpression system was constructed by infecting 786-O cells with viral particles carrying the CYFIP2 gene. The 786-O cells were used as the knockdown group (siRNA-CYFIP2, si-CYFIP2) after the CYFIP2 gene was knockdown, and set the corresponding control group si-NC; the 786-O cells were used as the overexpression group (Over Expression-CYFIP2, OE-CYFIP2) after performing CYFIP2 gene overexpression, and set the corresponding control group OE-NC.Subsequently, cell proliferation assays and Transwell assays were performed to analyze the differences in proliferative activity and migration ability of 786-O cells after knockdown or overexpression of CYFIP2 gene. Results The expression of CYFIP2 in KIRC was significantly lower (P<0.0001) in the TCGA database and decreased with the progression of tumor staging (P<0.05); CYFIP2 gene was also expressed at a low level after the occurrence of lymph node metastasis and distal metastasis (P_N<0.05, P_M<0.01); the 5-year survival rate of patients was significantly higher in the group with high CYFIP2 expression than that in the group with low expression (P<0.05). The cell proliferation activity assay showed that the proliferation activity was significantly enhanced in si-CYFIP2 group than that in si-NC group (P<0.0001) and the number of cell migration was significantly increased (P<0.0001), while the proliferation activity and migration ability of OE-CYFIP2 group were significantly inhibited (P<0.001) compared with that of OE-NC group. Conclusion The CYFIP2 gene had a significant inhibitory effect on the proliferation and migratory ability of KIRC cells and may have a potential antitumor effect, which can be one of the candidate genes for the subsequent clinical diagnosis and treatment of KIRC.

Lymph node noncompliance is an indicator. If multiple lymph node stations are not detected in each group of lymph nodes submitted for inspection, the specimen is regarded as lymph node noncompliance. Under the background that the incidence of advanced gastric cancer has been increasing year by year, more and more surgeons have begun to pay attention to the surgical effect of radical gastric cancer surgery and the prognostic quality of life of patients. A large number of domestic and foreign experimental studies have shown that the sequence of lymph node metastasis of gastric cancer is roughly from the lesser curvature of the stomach to the lymph nodes around the abdominal aorta. In addition, during the process of lymph node metastasis, there may be lymph nodes that do not appear in the specified location, or due to the factors such as the patient's advanced age, different surgical procedures, thick abdominal fat, deep tumor invasion, and more intraoperative bleeding, the D2 lymph node may be used for gastric cancer. During the resection operation and postoperative pathological sorting, certain errors occurred. Although radical resection of D2 lymph nodes has become a standard surgical approach for the treatment of advanced gastric cancer, a variety of congenital anatomical factors or human error factors will still cause a decrease in the detection rate of postoperative lymph nodes. Therefore, adequate D2 anatomy is still a research focus and difficulty for surgeons. This article discusses the research progress of lymph node noncompliance in D2 radical resection of advanced gastric cancer.

Objective To investigate the effect of activating peroxisome proliferator-activated receptor γ (PPARγ) on the expression of activator protein-1 (AP-1) and inflammatory response in lung tissues of mice infected with Mycobacterium tuberculosis(MTB). Methods A total of 50 healthy SPF C57BL/6 male mice aged 6 to 8 weeks were randomly divided into five groups (10 each group): control group, MTB group, MTB+Rosiglitazone group, MTB+GW9662 group, and MTB+ Rosiglitazone+GW9662 group. Lung tissue samples of mice were collected to detect the bacteria load. The protein and mRNA expression levels of PPARγ and AP-1 in lung tissues were detected by Western blotting and real-time fluorescent quantitative PCR (RT-qPCR). The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-10 and IL-6 in lung tissues were determined by enzyme-linked immunosorbent assay (ELISA). The pathological changes in the lung tissue of mice were observed by HE staining. Results Compared with MTB infection alone, PPARγ agonist rosiglitazone significantly increased the bacteria load in lung tissue of MTB-infected mice (P<0.05).Compared with control group, the expression of PPARγ and the content of inflammatory cytokines in the lung tissues of MTB infected mice were significantly increased, while the expression of AP-1 was significantly decreased, and the differences were statistically significant (P<0.05). When giving PPARγ agonist rosiglitazone at the same time as MTB infection, the expression level of AP-1 in lung tissue of mice was significantly decreased compared with MTB group (P<0.05). In addition, in MTB+Rosiglitazone group, the contents of IL-6 and TNF-α were (160.71±20.36) pg/ml and (343.55±58.48) pg/ml, respectively, both of which were down-regulated compared with MTB group [(232.59±21.73) pg/ml and (511.99±69.83) pg/ml]. Interestingly, the content of IL-10 in MTB+Rosiglitazone group [(105.97±10.38) pg/ml], significantly higher than that in MTB group [(83.25±9.00) pg/ml,P<0.05]. GW9662, a PPARγ antagonist, could reverse the above effects of rosiglitazone. Conclusion Activation of PPARγ can down-regulate the expression of AP-1 in the lung tissues of MTB-infected mice, thereby inhibiting the lung tissues inflammatory and affecting the clearance of MTB.

Kidney diseases have become an important public health problem worldwide that threatens human health. In addition to traditional risk factors such as advanced age, hypertension, and diabetes, environmental pollution, especially the air pollution and climate change, are also major risk factors for chronic kidney disease. The exposure of airborne particulate matter or gaseous pollutants has been found to be closely associated with the incidence of chronic kidney disease, decline of kidney function, and poor prognosis of patients. As the main manifestation of global climate change, climate warming could also lead to acute kidney injury and nephrolithiasis. This paper reviews the progress in the epidemiological research of the impacts of air pollution and climate change on kidney diseases, in order to provide reference for air pollution control, climate governance, and the development of prevention and control strategies for kidney diseases.

Objective To investigate the therapeutic effects of low-frequency ultrasound combined with 5-fluorouracil(5-FU) nanobubbles on post radiofrequency ablation (RFA) hepatocellular carcinoma (HCC) nude mice. Methods A xenograft HCC mouse model was established in 60 BALB/c nude mice (6-8 weeks) using human hepatocellular carcinoma cell lines (HepG2).The mice were randomized into four groups after RFA ablation of 80%: saline group, 5-fluorouracil loaded nanobubbles (5-FU)group, non-low frequency ultrasound irradiated 5-FU-loaded nanobubbles (non-low frequency ultrasound + 5-FU) group, and low-frequency ultrasound irradiated 5-FU-loaded nanobubbles (low-frequency ultrasound + 5-FU) group. The nude mice of the last three groups received a tail vein injection of 5-FU loaded nanobubbles (0.1 μg/μl), 200 μl each time, once every three days, and three consecutive injections. The low-frequency ultrasound + 5-FU group received additional irradiation of low-frequency ultrasound (1 MHz, 2 W/cm²) for 5 min after being injected into the nanobubble. The growing status, tumor size and survival time of nude mice bearing tumor in each group were observed and compared. At the end of the treatment, the tumor tissue was taken, apoptosis index was detected through the TUNEL method, and the tumor neovascular density (MVD) was detected by the CD34-MVD method. The apoptosis index and MVD values were compared in each group. Results After treatment, the nude mice in the different groups exhibited weight loss, a reduction in activity, appetite loss, and other symptoms to varying degrees. However, the growing status of tumor-bearing nude mice in low-frequency ultrasound + 5-FU group was significantly better than the other three groups. The tumor volume of nude mice in each group gradually increased. The tumor growth rate of low-frequency ultrasound+ 5-FU group was significantly lower than that of the other three groups, and the difference was statistically significant (P<0.05).The survival time of tumor-bearing nude mice in low-frequency ultrasound+5-FU group was significantly longer than that of the other three groups, and the difference was statistically significant (P<0.05). The apoptotic index of tumor cells in each group: low frequency ultrasound + 5-FU group (43.2%±4.4%) > non-low frequency ultrasound + 5-FU group (31.3%±4.3%) > 5-FU group(20.7%±2.9%) > saline group (10.8%±2.4%), and there were statistically significant in each group (P<0.05). Meanwhile, except for the low-frequency ultrasound + 5-FU group, multiple positive staining areas were seen in the tumors of the other three groups, and there were more positively stained tumor tissues. The MVD values (piece/HP) of each group: low frequency ultrasound + 5-FU group (8.9±1.3) < non-low frequency ultrasound + 5-FU group (20.1±3.2) <5-FU group (25.0±4.2) <saline group (29.9±2.0), and there were statistically significant in each group (P<0.05). Conclusions 5-fluorouracil loaded nanobubbles combined with low-frequency ultrasound could further improve drug targeting, effectively inhibit the growth of HCC, which can significantly inhibit residual cancer cells after RFA.

Intracranial aneurysm (IA), characterized by distended blood vessels within the arteries, is a common vascular anomaly that frequently leads to cerebral blood vessel rupture, causing subarachnoid hemorrhage (SAH) with serious consequences.It has been found that, in addition to genetic factors, inflammatory responses induced by altered hemodynamics play a key role in the formation and rupture of IA. Subsequently, vascular inflammation can trigger a series of biochemical responses involving a variety of cells, including vascular smooth muscle cells, macrophages, lymphocytes, mast cells, and neutrophils, and involving several signaling pathways, including the PGE2-EP2-NF-κB signaling pathway, the JAK/STAT3/NF-κB signaling pathway, PI3K/Akt (PKB) signaling pathway, and AMPK/ACC signaling pathway. However, no clear conclusions have been made regarding the specific pathogenesis of IA, and immunotherapies targeting the pathogenesis of IA are still under basic research and not widely used in clinical practice. This review describes the cells, cytokines, and signaling pathways involved in the development of IA, in the hope that it will contribute to the understanding of the pathogenesis of IA and inspire the development and use of immunological drugs.

Objective To report a case of refractory Takayasu arteritis (TAK) treated with tofacitinib (TOF) and evaluated by contrast-enhanced ultrasound, and perform a literature review to better understand this disorder. Methods The data of a case of TAK treated with TOF were analyzed retrospectively, the treatment and follow-up experience summarized by searching the database(CNKI, Wanfang Data, PubMed) and the literature results analyzed comprehensively. Results The patient, a 28-year-old female with a 10-year history of TAK, presented with fever, neck pain and joints pain. Ultrasonography revealed intimal thickening and stenosis of the carotid artery. Laboratory tests demonstrated an elevated erythrocyte sedimentation rate (ESR) and a C-reactive protein (CRP) level. The symptoms were improved after glucocorticoid (GC) treatment. However, it relapsed during the course of GC tapering, even with the combination of disease modifying anti-rheumatic drugs (DMARDs) and tocilizumab. The DMARDs and tocilizumab were not used continuously due to poor response and adverse drug reactions. As disease progressing, left subclavian aneurysm appeared. The treatment of this patient is a big challenge. After adjusting the treatment with tofacitinib (10 mg/d, then adjust to 7.5 mg/d) and GC (methylprednisolone 14 mg/d, then reduce to 8 mg/d), the patient was successfully relieved without any serious adverse events. Contrast-enhanced ultrasound showed that the thickness of arterial wall decreased (the thickness of left common carotid artery decreased from 8.9 mm to 1.2 mm, and the thickness of left subclavian artery decreased from 7.4 mm to 0.8 mm), the contrast intensity decreased (the total score decreased from 5 to 1), and the aneurysm disappeared. By March 2021 (searching CNKI, Wanfang Data and PubMed), a total of 10 cases of TAK patients treated with TOF. Nine patients were women. Seven patients improved and GC reduced. Only one patient had adverse reactions. Conclusions Janus kinase inhibitor is expected to be a new drug for the treatment of TAK. Contrast-enhanced ultrasound can detect the thickness of the vessel wall and the enhancement of the thickened wall in real time. Contrast-enhanced ultrasound will be an effective tool for evaluating vascular inflammation.

Objective To investigate the effect of AKT/mTOR and JAK/STAT pathways co-activation on axon regeneration and function recovery in C₅ spinal cord injury mice. Methods Forty adult C57/BL mice were randomly divided into PTEN/SOCS3 group (injected PTEN virus and SOCS3 virus), PTEN group (injected PTEN virus), SOCS3 group (injected SOCS3 virus) and control group (injected empty control virus), 10 mice in each group. Adeno-associated-virus (AAV) were injected into the sensorimotor cortex. The activation of AKT/mTOR and JAK/STAT pathways in pyramidal neurons was detected by measuring the expression of p-S6 and p-STAT3 using immunofluorescence staining. Two weeks after injection, all the mice received C₅ crush injury. Biotinylated dextran amine (BDA) tracer was used to label corticospinal tract. The horizontal ladder and cylinder rearing tests were used to assess motor function recovery at pre-injury, and one week, two weeks, four weeks and six weeks after injury. Results Immunofluorescence staining results showed that AAV successfully infected the sensorimotor cortex pyramidal neurons.The expression of p-S6 in PTEN/SOCS3 group and PTEN group were significantly increased, the fluorescence intensity of p-S6[(25.429±2.991) AU and (26.171±2.140) AU] were significantly higher than SOCS3 group and control group [(9.544±2.474) AU and (9.558±1.650) AU] (P<0.001). The expression of p-STAT3 in PTEN/SOCS3 group and SOCS3 group were obviously increased, compared with PTEN group and control group [(12.952±1.282) AU and (14.394±1.983) AU], the fluorescence intensity of p-STAT3 in PTEN/SOCS3 group and SOCS3 group [(48.900±6.310) AU and (46.721±5.169) AU] were significantly higher (P<0.001). Compared with control group, the other three groups showed obvious axon regeneration after corticospinal tract injury. The regeneration distance and number were longer and more in PTEN/SOCS3 group (P<0.05). There was no significant difference between four groups in horizontal ladder and cylinder rearing tests at various time points (P>0.05). Conclusion Co-activation of AKT/mTOR and JAK/STAT pathways could improve neurons intrinsic regenerative growth capacity and successfully promote axon regeneration in adult spinal cord injury mice, but could not have better early motor function recovery.

Objective To search for genes related to the occurrence and development of retinoblastoma (RB). Methods In this study, firstly, we obtained 3 gene expression datasets from the Gene Expression Omnibus (GEO) database. After they were merged, the sva package in R software was applied to remove the batch effects of these three datasets. The differentially expressed genes (DEGs) were identified by limma package. ClusterProfiler package was used to analyze GO enrichment and KEGG pathway of DEGs. STRING database and Cytoscape software were used to construct the protein-protein interaction network (PPI). CytoHubba was applied to find the hub gene of PPI network. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key modules associated with clinical information. The key genes of the key modules were further searched. Then, Y79, WERI-RB-1 and ARPE-19 cells were cultured in vitro, and the mRNA expression levels of five key genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 20 RB tissue samples were collected. Immunohistochemistry was used to detect the expression of key proteins. Results A total of 1254 DEGs were identified, among which 422 were up-regulated and 832 were down-regulated. In GO analysis, DEGs were mainly related to protein heterodimerization activity, cation transmembrane transporter activity, and chromatin binding. In KEGG analysis, DEGs were mainly enriched in cell cycle, phototransduction, and DNA replication. A total of 79 hub genes in the PPI network were obtained. In the co-expression network, DEGS were divided into 11 co-expressed gene modules. According to Pearson correlation coefficient between each module and clinical traits, 5 important modules including blue, pink, turquoise, red and brown were identified, among which blue module had the highest correlation coefficient with age at diagnosis (r=0.65). After comprehensive analysis, we obtained 5 hub genes including structural maintenance of chromosome 4(smc4), minichromosome maintenance complex component 6 (mcm6), centromere protein K (cenpk), kinesin family member 15(kif15), protein regulator of cytokinesis 1 (prc1). The qRT-PCR results showed that the mRNA relative expression levels of prc1 and cenpk in Y79/WERI-RB-1 cells were higher than those in ARPE-19 (P<0.05). Immunohistochemistry results indicated that PRC1 protein was higher expressed in RB tissue samples (P<0.05). Conclusion smc4, mcm6, cenpk, kif15, and prc1 were identified as hub genes by bioinformatics analysis, and the increased expression of PRC1 protein in RB may play an important role in the occurrence and development of RB.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of the respiratory tract that seriously affects lung ventilation function and gas exchange function. Mitochondria is the center of energy supply and signal induction in cells, which determine the survival and/or death of cells. The cell mitochondrial quality control mechanisms mainly include mitophagy, biosynthesis and dynamics (fusion/fission) and other regulatory processes. These cellular processes maintain the stability of quality and function of mitochondria by degrading aged and damaged mitochondria, replenishing new mitochondria, and promoting the exchange of mitochondrial contents. Recent studies have shown that mitochondrial quality control plays an important role in IPF. In IPF, the dysregulation of mitochondrial quality control leads to mitochondrial dysfunction, increased production of reactive oxygen species, inducing apoptosis, enhanced mitochondrial fusion, and decreased mitochondrial autophagy and biosynthesis. This review describes the research progress on abnormal mitochondrial quality control in IPF.