Objective By investigating the effects of miR-379-5p on the proliferation,invasion and metastasis of mouse breast cancer 4T1 cells,we aimed to provide new therapeutic targets for the clinical inhibition of breast cancer proliferation,invasion,and metastasis.Methods After plasmid transfection,4T1 cells were utilized to detect the expression of miR-379-5p using fluorescence quantitative PCR.While 5-ethynyl-2'doxyuridine(EdU)cell proliferation and Transwell assays were employed to detect changes in the proliferation and invasion ability of 4T1 cells in each group.The migration ability of 4T1 cells after overexpression and knockdown of miR-379-5p was examined by scratch healing assay.A transplanted tumor model of breast cancer was established in BABL/c mice,and the effects of overexpressing miR-379-5p on tumor growth and the number and size of lung metastases were observed.Results EdU result showed that knocking down miR-379-5p enhanced the proliferation ability of the cells compared with the control group cells,and miR-379-5p overexpression reduced the capacity of breast cancer cells to proliferate(P＜0.05).Transwell and wound healing assays showed that miR-379-5p knockdown enhanced,while miR-379-5p overexpression significantly inhibited,the invasion and migratory ability of breast cancer cells(P＜0.01).An in vivo tumorigenesis experiment with BABL/c mice showed that miR-379-5p overexpression significantly slowed the tumor growth rate(P＜0.05)and inhibited lung metastasis(P＜0.01).Conclusions MiR-379-5p plays a role in tumor gene suppression in breast cancer and inhibits the proliferation,invasion,and migration of mouse breast cancer 4T1 cells.

Objectives To explore the expression, biological function, and mechanism of MKI67 in pancreatic cancer and its clinical significance. Methods The expression level, diagnosis, and prognostic value of MKI67 in pancreatic cancer were analyzed using public databases. We also investigated the association between the MKI67 with immune cell infiltration and immune checkpoint molecules. We analyzed the functional pathway enrichment to uncover the possible molecular mechanisms. qRT-PCR and Western blot assay were used to verify the expression of MKI67 mRNA and protein. Immunohistochemistry staining was used to detect the expression of MKI67 in tissue protein. Results The high expression of MKI67 was significantly associated with high histological grades and poor outcomes in pancreatic cancer. High MKI67 expression was correlated with poor prognosis of pancreatic cancer patients (P=0.009). MKI67 was an independent risk factor for the patient outcome (95%CI: 1.084-1.743, P<0.05). The MKI67 expression was positively correlated with the helper T cell 2 levels but negatively correlated with plasmacytoid DC, NK cells, mast cells, the T follicular helper, immune DC, and CD8 T cells. Conclusion MKI67 may serve as a biomarker for the diagnosis and prognosis of pancreatic cancer and the mechanism might be associated with immune escape or immunosuppression.

Objective:Induced pluripotent stem cells (iPSCs) cell lines were established using peripheral blood mononuclear cells (PBMCs) from a patient suffering from neonatal respiratory distress syndrome (NRDS) who carried Adenosine triphosphate-binding cassette transporter A3 ( ABCA3) compound heterozygous mutations. Methods:Cell experimental research.Peripheral venous blood was collected and PBMCs were isolated and cultured in vitro. PBMCs were transfected with non-integrated Sendai vector carrying reprogramming factors.The chromosome karyotypes of the established iPSCs were analyzed.Immunofluorescence and flow cytometry were used to detect pluripotency markers of stem cells and verify their differentiation potential.Sanger sequencing was performed to analyze gene mutations.In addition, short tandem repeat (STR) analysis was performed, polymerase chain reaction(PCR) and agarose gel electrophoresis were used to detect virus residual. Results:Karyotype analysis of established iPSCs cell lines showed normal diploid 46, XY karyotype.Immunofluorescence showed positive staining of stem cell pluripotency markers OCT4, SSEA4, Nanog and Sox2.Flow cytometry was used to detected stem cell pluripotency markers and showed expression of TRA-1-60, SSEA-4 and OCT4.After differentiation into all three germ layers, immunofluorescence was performed to detect ectoderm (Pax-6), mesoderm (Brachyury) and endoderm alpha-fetoprotein markers, and the results showed positive staining, which confirmed that the iPSCs had the potential to differentiate.Sanger sequencing showed c. 3997_3998del and c. 3137C>T compound heterozygous mutations.STR analysis showed they originate from PBMCs, and no Sendai virus residual was detected by PCR and agarose gel electrophoresis.Conclusions:In this study, PBMCs from patient carrying ABCA3 compound heterozygous mutations was used to establish iPSCs cell lines.The research lays a foundation for the study of pathogenesis, therapeutic drug screening and cell therapy of NRDS caused by ABCA3 gene mutations.

Objective To investigate the effects of α7 nicotinic acetylcholine receptor (α7nAChR) on CD11b, IL-1β, IL-18 and TNF-α in acute respiratory distress syndrome (ARDS) mice. Methods A total of 40 healthy and clean male Balb/C mice (6 weeks old) were randomly divided into normal group (N group), normal saline control group (NS group), ARDS group (A group), and ARDS mice treated with nicotinic acetylcholine receptor agonist after bilateral cervical vagotomy group (J group), with 10 mice in each group. The right lung structure of mice in each group was observed by hematoxylin-eosin (HE) staining, the lung tissue wet weight/body weight ratio (LWW/DW ratio) was detected, and the percentage of CD11b in the alveolar lavage fluid of mice was detected by flow cytometry. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of IL-1β mRNA, IL-18 mRNA and TNF-α mRNA in left lung tissue. Serum IL-18 was determined by enzyme-linked immunosorbent assay (ELISA) and double antibody sandwich method. Results HE staining of the right lung of mice in group N and NS showed normal structure, while the lung interstitial of mice in group A showed a large number of inflammatory cells infiltrated, alveolar wall thickened, alveolar structure destroyed and alveolar cavity fused. The alveolar structure of mice in group J was intact, with a little damage and alveolar cavity. The percentage of CD11b in alveolar lavage fluid in group A was higher than that in the other three groups, and the difference was statistically significant compared with group N, NS and J, respectively (P<0.05). The expressions of IL-1β mRNA, IL-18 mRNA and TNF-α mRNA in the left lung of mice in group J were statistically significant compared with those in group N, NS and A (P<0.05), and the serum IL-18 level of mice in group A was higher than that in the other three groups, and the differences were statistically significant compared with groups N, NS and J, respectively (P<0.05). Conclusions Activation of α7nAChR can directly inhibit the release of CD11b in lung tissue and reduce the accumulation of inflammatory factors. Simultaneously, it can also directly inhibit the expression of IL-β1 mRNA, IL-18 mRNA and TNF-α mRNA in lung tissue and the release of IL-18, thus inhibiting the inflammatory response of ARDS and alleviating the pathological changes of ARDS.

Objective:To analyze the relationship between dietary composition of residents in endemic fluorosis areas and skeletal fluorosis.Methods:A case-control study was used to analyze the difference of dietary composition between patients with skeletal fluorosis (case group) and residents without skeletal fluorosis (control group). In August 2019, taking the drinking water-borne endemic fluorosis area in Wenshui County, Lvliang City, Shanxi Province as the survey site, a cluster sampling method was adopted to select local residents aged over 18 years old, and a questionnaire survey was conducted by face-to-face interview. The survey contents included gender, age and consumption frequency of various foods. Binary logistic regression was used to analyze the relationship between food consumption frequency and skeletal fluorosis. The diagnosis of skeletal fluorosis was made by using portable digital radiography (DR) to take X-ray films of forearm and lower leg, combining with clinical signs, and according to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008) to determine.Results:A total of 1 061 subjects were included in this study, including 376 in the case group and 685 in the control group. The age composition of patients in the case group (≤60, > 60 years old: 162, 214 cases) was significantly different from that in the control group (≤60, > 60 years old: 423, 261 cases, χ 2 = 34.52, P < 0.001). There was no statistically significant difference in gender ratio (χ 2 = 1.37, P = 0.251). The proportion of patients in the case group who ate meat and eggs > 1 time/week was lower than that in the control group (χ 2 = 8.06, 5.46, P < 0.05), the proportion of patients who ate milk > 1 time/week was higher than that in the control group (χ 2 = 4.01, P = 0.046), and the proportion of patients who ate seafood ≥1 time/week was lower than that in the control group (χ 2 = 4.16, P = 0.046). The results of binary logistic regression analysis showed that after adjusting for age, sex, and urinary fluoride, the frequency of eating meat, eggs or milk > 1 time/week and the frequency of eating seafood ≥1 time/week were not related to the risk of skeletal fluorosis ( P > 0.05); however, in the group ≤60 years old, the frequency of eating eggs > 1 time/week was associated with the risk of skeletal fluorosis [odds ratio ( OR) = 0.59, 95% confidence interval ( CI): 0.39, 0.88]. Conclusions:The consumption frequency of meat, milk, eggs and seafood is significantly different between the skeletal fluorosis patients and the control people. In the population ≤60 years old, consumption frequency of eggs > 1 time/week may reduce the risk of skeletal fluorosis.

Cachexia is a common complication in patients with lung cancer. It aggravates the toxic and side effects of chemotherapy, hinders the treatment plan, weakens the responsiveness of chemotherapy, reduces the quality of life, increases complications and mortality, and seriously endangers the physical and mental health of patients with lung cancer. The causes and pathogenesis of tumor cachexia are extremely complex, which makes its treatment difficult and complex. Controlling cachexia in lung cancer patients requires many means such as anti-tumor therapy, inhibition of inflammatory response, nutritional support, physical exercise, and relief of symptoms to exert the synergistic effect of multimodal therapy against multiple mechanisms of tumor cachexia. To date, there has been a consensus within the discipline that no single therapy can control the development of cachexia. Some therapies have made some progress, but they need to be implemented in combination with multimodal therapy after fully assessing the individual characteristics of lung cancer patients. This article reviews the application of drug therapy and nutritional support in lung cancer patients, and looks forward to the research direction of cachexia control in lung cancer patients.
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Cachexia/therapy* ; Combined Modality Therapy ; Humans ; Lung Neoplasms/drug therapy* ; Neoplasms/complications* ; Nutritional Support/adverse effects* ; Quality of Life

Non-alcoholic fatty liver disease (NAFLD) is a series of chronic liver diseases strongly associated with the metabolic disorder with an increasing rate of worldwide prevalence.Due to its complicated pathogenesis, only Saroglitazar has been approved by Indian Drug Controller General (DCGI) as a PPAR-α/γ dual agonist to treat non-cirrhotic non-alcoholic steatohepatitis.Combination therapy, which can target same or different signaling pathways of NAFLD pathogenesis, has been developed to achieve synergistic therapeutic efficacy.Currently, small-molecule drug combination, RNAi combination therapy, and chemogene therapy are proposed as promising strategies in NAFLD treatment.In addition, designing a smart, safe and effective drug delivery system is key to realizing the druggability, clinical translation and industrialization of small molecule drugs and gene drugs.This review summarizes the research status and delivery system of small-molecule drug combination, RNAi combination therapy, and chemogene therapy, in the hope of providing some novel insight for the treatment of NAFLD.

Objective:Through determination of urinary arsenic metabolites in high water arsenic exposed areas of Jilin and Shanxi provinces, to explore the mode and possible influencing factors of arsenic metabolism in different populations.Methods:From October 2018 to August 2019, a cluster sampling was carried out in villages (arsenic in drinking water ≥0.05 mg/L) of some townships (towns) in Lyuliang City, Shanxi Province and Baicheng City, Jilin Province for epidemiological investigation and general health examination. The residents over 35 years old drinking water from local centralized water supply and small well water sources were selected as arsenic exposure group, and people (nearby low-arsenic water source areas) with the same diet and living habits and similar economic conditions were selected as control group. Urine samples were collected. Liquid chromatography-atomic fluorescence spectrometry(LC-AFS) technology was used to separate and detect 4 species of arsenic compounds, including trivalent inorganic arsenic (iAs Ⅲ), pentavalent inorganic arsenic (iAs Ⅴ), methylated arsine (MMA), and dimethylated arsine (DMA). Total arsenic (tAs), inorganic arsenic percentage (iAs%), MMA percentage (MMA%), DMA percentage (DMA%), primary methylation index (PMI) and the secondary methylation index (SMI) were calculated. The influencing factors of arsenic metabolism were analyzed by multiple linear regression. Results:A total of 1 415 villagers were investigated, including 1 256 in arsenic exposure group and 159 in control group. Compared with the control group, there were no significant differences in age, gender ratio and occupation distribution between arsenic exposure group and control group ( P > 0.05), but there were significant differences in smoking, drinking, body mass index (BMI) and education level distribution ( P < 0.05). The median of urinary tAs, iAs%, MMA%, DMA%, PMI and SMI in control group and arsenic exposure group were 12.86 μg/L, 15.03, 5.23, 76.35, 84.97, 93.68 and 69.68 μg/L, 10.24, 8.37, 79.31, 89.76, 90.65, respectively, the levels of urinary tAs, DMA% and PMI in arsenic exposed group were higher than those in control group, while iAs% and SMI were lower than those in control group, the differences were statistically significant ( U=- 13.87, - 4.30, - 6.64, - 6.64, - 1.99, P < 0.05). After analysis of the factors influencing urinary arsenic metabolism in the population, we found that age and BMI had an impact on iAs% ( β=- 0.08, - 0.08, P < 0.05); gender, drinking, BMI and education level were influencing factors of MMA% ( β =- 0.11, - 0.09, - 0.07, 0.08, P < 0.05); DMA% was mainly affected by age, gender, BMI and education level ( β = 0.06, 0.09, 0.10, - 0.09, P < 0.05); PMI was mainly affected by age and BMI ( β = 0.08, 0.08, P < 0.05); while SMI was affected by gender, drinking, BMI and education level ( β=0.09, 0.08, 0.08, - 0.09, P < 0.05). Conclusions:The urinary arsenic metabolism models of different arsenic exposed groups are different. Age, gender, smoking, drinking, BMI and education level may be influencing factors of different arsenic metabolism models.

Objective:To study and explore the effect and mechanism of action of Jieduhuayu granules on oxidative injury of human liver L02 cells.Methods:Human liver L02 oxidative injury model was established with 0.1 mmol/ L H 2O 2 intervention for 1 h, and treated with different concentrations of Jieduhuayu (JDHY) solution. Hepatocytes were divided into five groups: normal, H 2O 2, H 2O 2 + JDHY (0.5 mg/ml), H 2O 2 + JDHY (1 mg/ml), and H 2O 2 + JDHY (1.5 mg/ml). MTT assay was used to detect hepatocytes activity. Transmission electron microscope was used to observe mitochondrial morphology in hepatocytes. Biochemical test was used to detect the levels of superoxide dismutase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and reduced glutathione and albumin in hepatocytes. Western blot was used to detect the expression levels of rabbit anti-phosphatidylinositol 3-kinase (PI3K), AKT and mTOR in hepatocytes. One-way analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison. Results:Compared with the normal group, the cell proliferation activity ( P < 0.05), mitochondrial vacuolization, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT, and mTOR protein expression levels in the H 2O 2 group were all significantly reduced ( P < 0.05), while the content of malondialdehyde and the activities of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were significantly increased ( P < 0.05). Compared with H 2O 2 group, the cell proliferation activity ( P < 0.05), alterations in morphological remission of mitochondria, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT and mTOR protein expression levels in the H 2O 2 + JDHY (1 mg/ml) and H 2O 2 + JDHY (1.5 mg/ml) group ( P < 0.05) were all significantly increased ( P < 0.05), while malondialdehyde content and alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities were significantly decreased ( P < 0.05). Conclusion:Jieduhuayu granule can effectively improve oxidative stress and mitochondrial injury in hepatocytes, and its effect may be related to the promoting expression of PI3K/AKT/mTOR signaling pathways.

Efficient and safe delivery of drugs, proteins or genes to the targeted sites has been the focus of pharmaceutical research. Inorganic nanomaterials are ideal materials for drug delivery systems due to their good stability, excellent biocompatibility and high drug loading capacity.Inorganic nanomaterials are ideal materials for drug delivery systems due to their good stability, high biocompatibility and excellent drug loading capacity. In this review, we started with reported researches and clinical trials to discuss the researches and clinical transformation of these inorganic nanoparticles in application of drug delivery, including carbon nanomaterials, silica nanoparticles, calcium nanomaterials, gold nanoparticles, magnetic nanoparticles, upconversion nanoparticles and quantum dots, providing theoretical reference for application of inorganic drug delivery carriers in the development of new drugs, looking to the prospects of inorganic nanomaterials in clinical application.