BACKGROUND: Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer, and any change of miRNAs expression will affect the degree of target regulation, thus affecting intracellular homeostasis. This study verified that miR-186-5p could inhibit the proliferation, migration and invasion of LUAD cells by regulating PRKAA2. METHODS: Previous investigations found that the expression of miR-186-5p was markedly suppressed in LUAD. Bioinformatics method is used to predict the target protein related to ferroptosis downstream and inquire about its expression level in LUAD and its influence on the survival of patients. Double luciferase verified the binding site of PRKAA2 and miR-186-5p. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression of PRKAA2. The effects of miR-186-5p of LUAD cells as well as the mechanism by which miR-186-5p inhibits Fer-1's sensitivity to ferroptosis were confirmed by EdU, Transwell, and scratch assays. The effect of miR-186-5p on the amount of reactive oxygen species (ROS) in LUAD cells was discovered using ROS experiment. Malondialdehyde (MDA) and glutathione (GSH) experiments were used to detect the effects of miR-186-5p and PRKAA2 on ferroptosis index of LUAD cells. The concentration of lipid ROS (L-ROS) in LUAD cells were measured using the L-ROS tests to determine the effects of miR-186-5p and PRKAA2. RESULTS: The expression of PRKAA2 is up-regulated, and a high level of PRKAA2 expression was associated with a poor prognosis for patients with LUAD. Overexpression of miR-186-5p decreased the gene and protein expression of PRKAA2. By promoting ferroptosis, miR-186-5p overexpression prevented lung cancer cells from proliferating, invading, and migrating. ROS could be produced in higher amounts in LUAD cells due to miR-186-5p. Overexpression of miR-186-5p and knockdown PRKAA2 up-regulated MDA content and reduced GSH content in LUAD cells, respectively. miR-186-5p could increase the content of L-ROS and promote the ferroptosis sensitivity of LUAD cells by targeting PRKAA2. CONCLUSIONS miR-186-5p promotes ferroptosis of LUAD cells through targeted regulation of PRKAA2, thus inhibiting the proliferation, invasion and migration of LUAD.
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Humans ; Lung Neoplasms/genetics* ; Carcinoma, Non-Small-Cell Lung ; Ferroptosis/genetics* ; Reactive Oxygen Species ; Adenocarcinoma of Lung/genetics* ; MicroRNAs/genetics* ; 3,4-Methylenedioxyamphetamine ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor ; AMP-Activated Protein Kinases

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common clinical histological subtype of lung cancer and microRNAs (miRNAs) are a type of small non-coding RNAs which play a central role in cells. miR-30b-3p plays a key effect in many types of carcinoma, but there is still very little research on how it works in lung adenocarcinoma. The role and mechanism of miR-30b-3p in the proliferation and invasion of LUAD were explored in this study, to provide new targets for inhibiting the proliferation and invasion of LUAD. METHODS: NCBI database was used to screen out miRNA with obvious differential expression, and the differential expression and survival curve were searched by StarBase database. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expression of miR-30b-3p in each lung adenocarcinoma cell line. 5-ethynyl-2'-deoxyuridine (EdU) cell proliferation assay and Transwell invasion assay were used to detect the proliferation and invasion of A549 cells in each group. The target genes of miR-30b-3p were determined by the target gene prediction websites. Western blot assay was used to detect the expression of COX6B1 in each group of A549 cells. Double luciferase assay was used to verify the targeted binding relationship between miR-30b-3p and COX6B1. RESULTS: The expression of miR-30b-3p in lung adenocarcinoma tissues and lung adenocarcinoma cells was downregulated (P<0.05). Low expression levels of miR-30b-3p were associated with poor prognosis in patients with lung adenocarcinoma (P=0.005,8). Overexpression of miR-30b-3p could inhibit the proliferation and the invasion of lung adenocarcinoma cells (P<0.05). Double luciferase assay proved that miR-30b-3p could target and bind to COX6B1 (P<0.05). Western blot analysis showed that the overexpression of miR-30b-3p could downregulate the expression of COX6B1 in A549 cells (P<0.05). EdU cell proliferation assay and Transwell invasion assay showed that the overexpression of miR-30b-3p could reverse the promoting effect of upregulation of COX6B1 on proliferation and invasion in lung adenocarcinoma cells (P<0.05). CONCLUSIONS miR-30b-3p acts as a tumor suppressor gene in lung adenocarcinoma, and it can inhibit the proliferation and invasion of lung adenocarcinoma by targeting the expression of COX6B1.
Adenocarcinoma of Lung/pathology* ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/pathology* ; MicroRNAs/metabolism*

" Two-way referral, and synergy between the tertiary hospitals and primary institutions" is the core measure for promoting hierarchical diagnosis and treatment in the region. The authors introduced the exploration and practice of constructing a two-way referral path in the medical alliance based on telemedicine in West China Second University Hospital of Sichuan University. As of May 2021, the hospital had established a two-way referral path with 52 member hospitals of the medical alliance. By clarifying the functionality and positioning of these institutions, optimizing work processes and IT support, building the mechanism of referral and liaison, and that of appraisal as support, these efforts had achieved progresses in such fields as innovative medical service modes, lean management of referral processes, and promotion of hierarchical diagnosis and treatment system building.

As one of the main forms of the medical alliance, the specialty alliance functions as a service carrier for hierarchical medical service and resources integration in the region. The authors introduced the exploration and practice of the West China Women′s and Children′s Alliance, the first pediatric specialty alliance in Sichuan, established by the West China Second Hospital of Sichuan University. Based on family doctor contracted services, the West China Women′s and Children′s Alliance took such measures as differentiated functional positioning, assessment of certified physicians, continuous online quality control, construction of referral platforms, and innovative payment mechanisms. Such efforts effectively integrated the three stages of pre-hospital " preventive care" , in-hospital " disease diagnosis and treatment" , and post-hospital " follow-up management" , exploring the homogenization of medical services within the alliance, and forming a pediatric closed-loop health management system, hence improving the primary medical services.

Colorectal cancer is one of the common malignant tumors,and its morbidity and mortality are in the third and fourth places,respectively. About 60% of patients are in an advanced stage at the diagnosis,and their 5-year survival rate is around 13% . In the past 20 years,since the standardized application of advanced first-line chemotherapy and targeted drugs for metastatic colorectal cancer(mCRC),mCRC treatment has made a major breakthrough. The use of oxaliplatin,capecitabine,bevacizumab,cetux-imab and other drugs have doubled the median survival and increased the 5-year survival rate by 20% . The usual mode of first-line treatment of mCRC in the late stage is continuous medication until the disease progress or the intolerable toxicity occurs. However,be-cause of the accumulation of toxicity of chemotherapy drugs,only one-third of patients can continue to receive treatment until the dis-ease progresses. After completing established initial treatment cycle and achieving CR/PR/SD,the patients continue to use low -dose,low-toxic drugs for maintenance treatment,which can delay the progression and metastasis of the tumor,and reduce the side effects of drug. At present,maintenance therapy has become the main treatment mode after advanced first -line chemotherapy for mCRC. However,the optimal maintenance regimen for mCRC remains inconclusive,and existing maintenance regimens still do not find a balance between optimal outcome and maximum quality of life. This article will review the clinical studies of mCRC′s existing main-tenance treatment regimens,summarize the current status of mCRC maintenance therapy,and discuss individualized treatment strate-gies.

Objective The SNPs of caspase family have been studied in breast cancer,head and neck cancer,esophageal cancer,lung cancer and other cancer. There are few studies between the SNP of CASP3,7 and the risk of gastric cancer in Chinese population. The aim of this study was to investigate the relationship between the SNP of CASP3,7 genes and the genetic susceptibility of gastric cancer using large samples. Methods Blood samples from 1000 cases of gastric cancer and 1036 cases of normal non-cancer control in Northeast China were collected for genomic DNA extraction. Based on the dbSNP NCBI database and HapMap data-base,potential SNP sites were selected for CASP3,7,which locate CASP3,CAS′s 3′UTR. The Tasman probe method was used for gen-otyping of the SNP sites of CASP3,7. The difference between the different variables in the case-control group was analyzed by the bi-lateral χ2 test. After the Hardy-Weinberg genetic balance test for each locus,the χ2 test was used to compare the genotype frequency differences between the case and control groups. Univariate and multivariate logistic regression models were used to analyze the associ-ation between genotype and disease. The stratification analysis of each locus compared the genotypes between the different sexes,ages, smoking,and drinking status. Results The χ2 test compared the differences between the case and control groups. The results showed that there was a significant difference in the smoking,drinking status and smoking in packet number( Pack-years) between the case and control groups(P<0. 05). The genotype frequencies of selected loci were in accordance with Hardy-Weinberg′s law of genetic balance(P>0. 05). Combining and analyzing genotypes with risk alleles,there showed that individuals with two risk genotypes in- creased by 69. 6% in comparison with individuals with 0~1 risk genotype. After adjusted for covariate effects,individuals with three risk genotypes were increased by 27. 6% when compared to individuals with 0~1 risk genotypes. Individuals with more than one risk genotype were increased by 35% when compared to individuals with 0-1 risk genotypes. In the stratified analysis,after combination of two genes,the risk genotype in the sub-layer of age ≤60 years old,male,never smoking,annual smoking package ≤25,gastric non-cardiac adenocarcinoma was statistically associated with disease,i. e. more risk of gastric cancer. Conclusion Univariate analy-sis showed that the SNPs at the four sites selected in this study were not associated with the risk of gastric cancer. However,multivari-ate analysis of CASP3 and CASP7 at the four sites showed that individuals with two risk genotypes increased the risk of gastric cancer in comparison with individuals with 0~1 risk genotypes. In addition,after stratified analysis of the two sites of CASP7,the risk of gas-tric cancer is more obvious in people aged≤60 years,never smoking or smoking≤25 packs per year,and non-gastric cardia adeno-carcinoma.

Objective The aim of this study was to explore the expression of constitutive photomorphogenesis factor 9 signa-ling complex subunit 6(CSN6) in hepatocellular carcinoma( HCC),and its clinicopathological factors and prognosis. Methods The expression of CSN6 at levels of protein and mRNA in hepatocellular carcinoma and normal hepatic tissues was analyzed using public human protein Atlas database and StarBase database. The TCGA database was used to analyze the differential expression of CSN6 in patients with different tumor stages and graded of hepatocellular carcinoma. Immunohistochemistry was used to detect the expression of CSN6 protein in 106 patients with HCC and analyzed its relationship with multiple clinicopathological factors and overall survival. Results The expression of CSN6 was elevated in hepatocellular carcinoma tissues when compared to normal hepatic tissues. CSN6 was more highly expressed in patients with high pathological grades(G3 and G4)and high stages (Ⅱ and Ⅲ);patients with hepato-cellular carcinoma with high expression of CSN6 had a shorter overall survival. The expression of CSN6 in hepatocellular carcinoma was associated with tumor differentiation and hepatitis B virus infection, and was an independent predictor of overall survival. Conclusion The expression of CSN6 is significantly increased in hepatocellular carcinoma. The increased expression of CSN6 in HCC tissues suggests a poor prognosis. The increased expression is associated with the malignant progression of hepatocellular carcino-ma and has a potential new prognostic marker and therapeutic target.

Antiangiogenic targeted therapy plays an important role in the treatment of malignant tumors,especially in the process of antitumor treatment including transformation stage,late stage,and maintenance stage.Apatinib(YN968D1)is a self-developed antian-giogenic targeted agent that was approved and launched for third-line and subsequent-line treatment for advanced gastric adenocarci-noma or gastro-esophageal junction adenocarcinoma.Moreover,the use of apatinib for other multiple solid tumors has been investi-gated.With an increase in the number of clinical studies on apatinib,concerns have been raised about its safety.Hence,we highlight the common adverse reactions of apatinib in clinical application and the incidences of various adverse events in different tumor treat-ments.We provide a comprehensive analysis of available clinical data and compare the advantages and disadvantages of apatinib with other common antiangiogenic drugs regarding their adverse reactions.Overall,these results will help to provide a better understand-ing of the safety of this medicine in the hope of helping physicians to provide patients with a safe and effective treatment.

OBJECTIVE: To prepare zedoary turmeric oil compound liposomes (ZTOC-LPS) and evaluate its quality.METHODS: The preparation method of liposome, the addition amount of soybean phosphatidylcholine (SPC), ratio of SPC to cholesterol (CH) in lipid, drug-lipid ratio of zedoary turmeric oil (ZTO), drug-lipid ratio of tretinoin in formulation, and water bath temperature were screened using encapsulation efficiency and drug-loading amount of ZTO (represented by germacrone) and tretinoin as investigation indexes. Quality evaluation and primary stability investigation were conducted for liposomes prepared by optimal preparation technology. RESULTS: The optimal preparation method was ethanol injection method; The optimal preparation technology were SPC 4 mg in 1 mL lipid, the mass ratio of SPC to CH 3:1, the ratio of ZTO to lipid 1:9, the ratio of tretinoin to lipid 1:70, water bath temperature of 55 ℃. Encapsulation efficiencies of ZTO and tretinoin were (64. 63 ± 1. 00)％ and (90. 33 土 0. 72)％ in 3 batches of ZTOC-LPS, respectively. Drug-loading amount of ZTO and tretinoin were (9. 09 ± 0. 14)％ and (1. 43 ± 0. 02)％, respectively. Particle size was (257. 41 ± 7. 58) nm, Zeta potential was (-38. 77 ± 0. 81) mV,PDI was 0. 10 ± 0. 04; the results of centrifugal acceleration test showed that the liposomes had good physical stability. No obvious change was found in each investigation index of ZTOC-LPS that stored at (4 ± 2) ℃ for 1 month. CONCLUSIONS: Established preparation technology is simple and feasible, the quality of the prepared ZTOC-LPS conforms to the requirements, and it can provide reference for the following research of ZTOC-LPS.

Objective To investigate the clinical effect of paraquat (PQ) detoxification recipe combined with continuous hemoperfusion (HP) in the treatment of patients with acute paraquat poisoning (APP) and clinical significance of soluble CD14 subtype (sCD14-st, Presepsin). Methods A prospective randomized controlled trial was conducted. 152 patients with moderate APP admitted to Department of Emergency Medicine of Harrison International Peace Hospital Affiliated to Hebei Medical University from July 2013 to June 2017 were enrolled, and they were randomly divided into three groups. The patients in HP group (group A, n = 35) only received 2-hour HP for 3 times, 8 hours each time, those in PQ detoxification recipe combined with HP group (group B, n = 50) received PQ detoxification recipe 1 (once per 2 hours until no PQ component was found in faeces) and 2 (3 times a day for 14 days) beside HP. The others in PQ detoxification recipe combined with persistent HP group (group C, n = 67) received continuous HP until the PQ component in serum was not detected. The parameters of organ function and inflammatory factor, and blood Presepsin and PQ contents were determined before and after treatment. The curative effect and 28-day mortality were recorded. The correlations between serum Presepsin level and PQ content as well as 28-day mortality were analyzed with Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of Presepsin on prognosis. Results The total effective rate of group C was significantly higher than that of groups A and B [70.1% (47/67) vs. 34.3% (12/35), 54.0% (27/50)], and 28-day mortality was significantly lowered [29.8% (20/67) vs. 65.7% (23/35), 46.0% (23/50), both P < 0.05]. There was no significant difference in alanine aminotransferase (ALT), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukins (IL-6 and IL-10) before treatment among the three groups. Five days after treatment, the above parameters in the three groups were increased as compared with those before treatment, but the increase degree in group C was the lowest. At 7 days after treatment, the parameters were decreased, especially in group C. There was no significant difference in serum Presepsin and PQ levels before treatment among the three groups. With the prolongation of treatment time, the Prespsin levels in groups A, B, and C were increased, and peaked at 12 hours (μg/L: 4.28±0.20, 3.87±0.25, 3.53±0.23), then gradually decreased,and the PQ contents were lower than those before treatment from 8 hours (mg/L: 1.76±0.12 vs. 2.12±0.17, 1.57±0.08 vs. 2.24±0.16, 1.25±0.10 vs. 2.14±0.18), with a time dependence pattern, especially in group C (all P < 0.05) . Correlation analysis showed that blood Presepsin level was positively correlated with PQ content and 28-day mortality (r1= 0.917, r2= 0.864, both P = 0.001), suggesting that the higher the PQ content was, the higher the Presepsin level, and the higher the 28-day mortality was. ROC curve analysis showed that the area under ROC curve (AUC) of Presepsin predicting 28-day mortality was 0.863; when the cut-off value was 1.22 μg/L, the sensitivity was 83.3%, the specificity was 81.4%, the positive predictive value was 77.46%, and the negative predictive value was 86.42%. Conclusions Early administration of PQ detoxification recipe combined with continuous HP treatment can effectively reduce Presepsin level, decrease the mortality of patients with moderate APP, improve the prognosis. Presepsin can assess the prognosis of patients with APP.