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.

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.

Objective To investigate the effect of fatty acid binding protein 4 (FABP4) in cardiomyocyte pyroptosis induced by homocysteine (Hcy). Methods The cultured rat cardiomyocytes were divided into two groups: control group(0 mmol/L Hcy) and Hcy group (3 mmol/L Hcy). The expression of FABP4 and pyroptosis related proteins [NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β)] were detected by Western blotting. The expression level of FABP4 mRNA was detected by qRT-PCR. The changes of expression of pyroptosis associated proteins were detected by immunofluorescence staining. The cultured cardiomyocytes were treated with FABP4 inhibitor (BMS-309403), and then divided into control group (0 mmol/L Hcy), Hcy group (3 mmol/L Hcy) and Hcy+BMS-309403 group (3 mmol/L Hcy and 50 μmol/L BMS-309403), and the expression levels of pyroptosis related proteins were then re-detected. Results Compared with control group, Western blotting showed that the expression levels of FABP4, NLRP3, caspase-1 and IL-1β in Hcy group increased significantly (P<0.05); Compared with control group, qRT-PCR results showed that the expression of FABP4 in Hcy group increased significantly (P<0.05); Compared with control group, immunofluorescence staining results showed that the fluorescence intensity of NLRP3, caspase-1 and IL-1β in Hcy group increased significantly. After adding FABP4 inhibitor (BMS-309403) and Hcy treatment, the expression levels of FABP4, NLRP3, caspase-1 and IL-1β in Hcy+BMS-309403 group decreased significantly compared with Hcy group (P<0.05 or P<0.01). Conclusion FABP4 may promote cardiomyocytes pyroptosis induced by homocysteine.

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 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.

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.

Objective To investigate the changes of serum markers of cardiovascular disease risk in patients with acromegaly and the effect of six months of treatment with long-acting octreotide on them. Methods The clinical data of 63 patients with acromegaly (acromegaly group) and 69 healthy people (control group) treated in the First Affiliated Hospital of Chongqing Medical University from May 2012 to January 2021 were collected and analyzed retrospectively. According to the blood glucose level, the patients with acromegaly were divided into three subgroups: normal glucose metabolism (NGT) group (n=25), Impaired glucose regulation (IGR) group (n=11) and diabetes mellitus (DM) group (n=27). The age, body mass index (BMI), blood pressure, growth hormone (GH), blood glucose, blood lipid, high-sensitivity C-reactive protein (hs-CRP), fibrinogen and plasma atherogenic index(AIP) between acromegaly group and control group and three glucose metabolism subgroups were compared, and the relationship between age, BMI, blood pressure, fibrinogen, hs-CRP, blood lipid and AIP was analyzed by Spearman correlation analysis.In addition, 16 of 63 patients with acromegaly who finally completed 6-month long-acting octreotide treatment were studied longitudinally, and the changes of the indexes above were compared before and after treatment. Results Compared with the control group, the levels of BMI, blood pressure, fibrinogen, fasting blood glucose (FPG), triglyceride (TG), lipoprotein a [Lp (a)]and AIP were significantly higher, and of hs-CRP, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were significantly lower (P<0.05) in acromegaly group. For subgroup analysis, the TG level was significantly higher in DM group than that in IGR group and NGT group (P<0.05), while the difference between IGR group and NGT group was not statistically significant; The AIP level was significantly higher in DM group than that in NGT group (P<0.05), and no significant difference existed among the other groups. In correlation analysis, AIP was positively correlated with BMI, fibrinogen, FPG, TG, apolipoprotein B (Apo B), non-high density lipoprotein cholesterol (Non-HDL-C), TC/HDL-C, LDL-C/HDL-C, APO B/APO A-1, and Non-HDL-C/HDL-C, but negatively correlated with HDL-C and apolipoprotein A-1 (Apo A-1). After subgroup analysis, AIP was still correlated with the indexes mentioned above, and the difference was statistically significant (P<0.05). The levels of TG and AIP decreased significantly, but of hs-CRP increased significantly (P<0.05) in patients with acromegaly after 6 months of long-acting octreotide treatment compared with that before treatment. Conclusions The cardiovascular risk of patients with acromegaly is increased. Long acting octreotide treatment can reduce the risk of cardiovascular disease in patients with acromegaly.

Objective To evaluate the diagnostic value of magnetic resonance imaging (MRI) and mammography (MG)in clustered calcification of breast lesions. Methods The imaging and pathological data of 62 patients with clustered calcification breast lesions in the Chinese PLA General Hospital was retrospectively analyzed to compare the diagnostic efficacy of MRI and MG. Results Of 62 clustered calcification lesions, 20 were benign according to pathologic result, and 42 were malignant. In MRI examination, 14 cases (22.6%) were classified as 1-3, 11 cases (17.7%) as 4, and 37 cases (59.7%) as 5. In MG examination, 10 cases (16.1%) were classified as 1-3, 30 cases (48.4%) as 4, and 22 cases (35.5%) as 5. The consistency between MRI and MG was poor (Kappa=0.346). The diagnostic efficacy of MRI (AUC=0.940, 95%CI 0.850-1.000) was higher than that of MG (AUC=0.800,95%CI 0.686-0.914), and the sensitivity, accuracy, positive predictive value, negative predictive value of MRI (85.7%, 88.7%, 97.3%,76.0%) were higher than those of MG (50.0%, 64.5%, 95.5%, 47.5%). Conclusion For clustered calcification of breast lesions, the diagnostic value of MRI is higher than that of MG.

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.

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.