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AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.
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The diagnostic reference level (DRL) for adults radiation dose in CT examination based on a large-scale national survey data is released in the form of national health industry standards (WS/T 637-2018) after more than ten years of exploration by radiologists, imaging technologists, radiation protection specialists and radiographers. Its principles and method are in line with international practices and the actual situation in China, which basically cover frequently-used CT examination items for adults. Compared with DRL in several other countries or organizations, radiation exposure to the patients as a whole is at a reasonably low level. The 50th percentile (achievable dosimetry levels) and 25th percentile (indicative level of unusually low dosimetry) are given as additional tools for radiation dose optimization guidance. In daily activities of radiological diagnosis, the radiation dose should be matched with image quality and clinical diagnostic tasks, and the frequency of unjustifiable high or low radiation dose should be reduced.
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The diagnostic reference level (DRL) for adults radiation dose in CT examination based on a large-scale national survey data is released in the form of national health industry standards (WS/T 637-2018) after more than ten years of exploration by radiologists,imaging technologists,radiation protection specialists and radiographers.Its principles and method are in line with international practices and the actual situation in China,which basically cover frequently-used CT examination items for adults.Compared with DRL in several other countries or organizations,radiation exposure to the patients as a whole is at a reasonably low level.The 50th percentile (achievable dosimetry levels) and 25th percentile (indicative level of unusually low dosimetry) are given as additional tools for radiation dose optimization guidance.In daily activities of radiological diagnosis,the radiation dose should be matched with image quality and clinical diagnostic tasks,and the frequency of unjustifiable high or low radiation dose should be reduced.
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Objective@#To investigate the expression level of antisense transcript of pseudogene, general transcription factor Ⅱi psedugen23 (GTF2IP23), in breast cancer and its effect on the host gene general transcription factor Ⅱi (GTF2I).@*Methods@#The expressions of GTF2IP23 and GTF2I were detected in 40 cases of invasive breast cancer tumors and their counterparts by using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of GTF2IP23 on the expression of GTF2I gene and cell proliferation and migration were analyzed by overexpression of GTF2IP23 in breast cancer cells.@*Results@#The expression of GTF2IP23 mRNA in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.001), while the expression of GTF2I mRNA was significantly lower than that in adjacent tissues (P=0.007). The expression of GTF2IP23 was negatively correlated with GTF2I (r=-0.335, P=0.025). The expression of GTF2IP23 in breast cancer cells was significantly higher than in normal breast cells (P<0.01), while GTF2I expression in breast cancer cells was significantly lower than that in normal breast cells (P<0.01). Overexpression of GTF2IP23 in ZR-75-30 cells significantly reduced the expression of GTF2I (P=0.034) and enhanced cell proliferation (P=0.017) and migration (P=0.026) capacity.@*Conclusions@#GTF2IP23 is distinctly upregulated in breast cancer, it inhibits the expression of real gene GTF2I and promotes the proliferation of breast cancer cells.
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Objective To evaluate the effect of metformin on an imiquimod-induced psoriasis-like mouse model,and to explore its related mechanism.Methods A total of 50 male Balb/c mice were randomly divided into several groups:control group,imiquimod group (IM group) and imiquimod combined with metformin group (IM-Met group).The IM-Met group were classified into 3 subgroups (100,150 and 200 g/L IM-Met groups) according to the concentration of metformin.Mice in the control group were treated with topical vaseline cream on the back and intraperitoneal injection of 0.9％ sodium chloride physiological solution of 0.3 millilitres every day.Mice in the IM group were treated with topical imiquimod cream on the back and intraperitoneal injection of 0.9％ sodium chloride physiological solution of 0.3 millilitres every day.Mice in the 100,150 or 200 g/L IM-Met groups were treated with topical imiquimod cream on the back and intraperitoneal injection of 100,150 or 200 g/L metformin of 0.3 millilitres respectively every day.The changes of the erythema area,scales and psoriasis area and severity index (PASI) over time in each group were observed by naked eyes.These mice were sacrificed after 7 days of treatment.Western blot analysis was performed to determine the protein expression of interleukin (IL)-17 and phosphorylated signal transducer and activator of transcription 3 (p-Stat3) in the dorsal skin tissues of these mice,and enzymelinked immunosorbent assay (ELISA) to detect serum levels of IL-17,IL-6 and tumor necrosis factor-α (TNF-α) in these mice.Comparison among these groups was carried out by using one-way analysis of variance,and means of two groups were compared by using least significant difference (LSD)-t test.Results Compared with the IM group,the 100,150 and 200 g/L IM-Met groups showed alleviated erythema and scaling severity,and significantly decreased PASI score,protein expression of IL-17 and pStat3,and serum levels of inflammation factors such as IL-17,IL-6 and TNF-α (all P ＜ 0.05).Seven days later,the PASI score and protein expression of IL-17 and p-Stat3 were all significantly lower in the 150 g/L IM-Met group than in the 100 g/L IM-Met group (t =4.18,-5.95,-2.80 respectively,P ＜ 0.05,≤ 0.01,≤ 0.01 respectively),but no significant differences were observed between the 150 g/L IM-Met group and 200 g/L IM-Met group (t =0.29,-0.42,-0.32 respectively,P ＞ 0.05,=0.69,=0.76 respectively).The serum levels of IL-17,IL-6 and TNF-α in the 150 g/L IM-Met group were 33.388 ± 1.556 ng/L,210.741 ±4.440 ng/L and 249.434 ± 8.594 ng/L respectively,which were significantly higher than those in the 200 g/L IM-Met group (26.720 ± 2.156 ng/L,174.997 ± 9.501 ng/L,193.034 ± 6.661 ng/L respectively;t =7.93,10.79 and 16.403 respectively,all P ＜ 0.05),but significantly lower than those in the 100 g/L IM-Met group (44.008 ± 1.722 ng/L,260.926 ± 7.724 ng/L,271.409 ± 3.037 ng/L respectively;t =-14.47,-17.81 and -7.62 respectively,all P ＜ 0.05).Conclusion Metformin can alleviate psoriasis-like skin lesions and inflammation status in the imiquimod-induced psoriasis-like mouse model to a certain extent,which may be related to the decrease of p-Stat3 protein expression.
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Objective To investigate the features of Langerhans cell histiocytosis (LCH). <b>Method</b> Skin lesions,systemic involvement,imaging characteristics,laboratory tests,immunophenotying,treatment response,and survival of 122 LCH patients treated at our center from February 1983 to August 2013 were retrospectively analyzed. Results LCH was associated with diverse skin lesions. Lung was the most involved organ,followed by bone,skin,lymph nodes,liver,spleen,oral cavity,and thyroid. Multisystem LCH was more common than single-system LCH. Single-system LCH was mostly treated by surgery,whereas multisystem LCH by combined chemotherapy. Conclusion LCH has diverse clinical manifestations,with lungs being the most often involved organ. Surgery or chemotherapy is the mainstream treatment.
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ObjectiveTo investigate the expressions ofheparinase,matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2(TIMP2) in malignant melanoma lesions and their significance.MethodsSkin specimens were obtained from the lesions of 30 patients with malignant melanoma,30 patients with melanocytic nevus and the normal skin of 15 healthy controls.Immunohistochemical SP method was used to detect the protein expression of heparinase,MMP2 and TIMP2.ResultsThe malignant melanoma tissue specimens significantly differed from the melanocytic nevus and control tissue specimens in the expression rate of heparinase (63.33％ vs.6.67％ and 0.00,x2 =21.172,27.805,both P ＜ 0.01 ),MMP2 (70.00％ vs.13.33％ and 0.00,x2 =19.817,19.866,both P＜ 0.01) and TIMP2(60.00％ vs.6.67％ and 0.00,x2 =19.200,15.000,both P ＜ 0.01 ).ConclusionThe expression of heparinase,MMP2 and TIMP2 is significantly higher in malignant melanoma lesions than in melanocytic nevus lesions and normal skin tissue.
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Objective To investigate the expressions of stern cell markers CD133,nestin and CD44 in malignant melanoma and their significance.Methods Tissue samples were obtained from 30 patients with malignant melanoma and 30 patients with intradermal nevus.The expressions of three markers were immunohistochemically detected in the samples.Results In malignant melanoma specimens,the expression rate of CD133,nestin and CD44 was 53.33%(16/30),80.00%(24/30)and 20.00%(6/30),respectively,significantly difierent from that in intradermal nevus specimens [23.33%(7/30),53.33%(1 6/30)and 0,respectively,all P＜0.05].The percentage of cells positive for CD133,nestin and CD44 was 2.98%±5.62%,34.92%±34.89%and 1.28%±3.26%,respectively,in malignant melanoma specimens.0.10%±0.21%,7.26%±13.13%and 0,respectively,in intradermal nevus specimens;there was a significant difierence between the two groups of specimens(all P＜0.05).In malignant melanoma and intradermal nevus,the expression intensity of CD133.nestin and CD44 showed no significant correlation with patients'sex.age or disease course(all P＞0.05).ConclusionsCD133,nestin and CD44 are highly expressed in malignant melanoma,but weakly expressed or absent in intradermal nevus,suggesting that tumor stem cells might exist in malignant melanoma tissue.