Effect of Qiyu Sanlong Decoction in Inhibiting Growth of Lung Cancer by Regulating Expressions of Beclin1, Atg5 and LC3B / 中国实验方剂学杂志

Objective::To study the effect of Qiyu Sanlong decoction on the growth of subcutaneous tumor in lung cancer mice and the expressions of key autophagy molecule, yeast Atg6 homologous (Beclin1), autophagy related genes5 (Atg5), and microtubule-associated protein1 light chain3 (LC3B). Method::Lewis lung carcinoma cells (LLC) were used to reproduce the lung cancer mice transplanted model. After the modeling, the mice were randomly divided into model group, Qiyu Sanlong decoction group, chemotherapy group and combination group, with 18 transplanted mice in each group. In model group, mice were fed with 0.9% saline 20 mL·kg-1 daily. In Qiyu Sanlong decoction group, mice were fed with Qiyu Sanlong decoction 80.48 g·kg-1 daily. The chemotherapy group was intraperitoneally injected with 0.4 mL cisplatin solution (DDP) at the 1st, 3rd and 5th day. The combination group was orally given the drugs at the concentration of 80.48 g·kg-1, and 0.4 mL DDP solution was intraperitoneally injected at the 1st, 3rd and 5th day. After 21 days of continuous treatment, tumor tissue was exfoliated and weighed, and the tumor inhibition rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the histological changes of tumor. The expressions and localizations of Beclin1 and LC3B in tumor tissues were detected by immunohistochemical staining. Protein expressions of Beclin1, Atg5, LC3B-Ⅰand LC3B-Ⅱ were determined by Western blot, and the ratio of LC3B-Ⅱ/LC3B-Ⅰ was calculated. The transcription levels of Beclin1, Atg5 mRNA in tumor tissues were detected by Real-time PCR. Result::Qiyu Sanlong decoction had a mild inhibitory effect on transplanted tumor, with an inhibitory rate of 31.2%. Under microscope, patchy necrotic tumor cells were observed in the tumor tissues of Qiyu Sanlong decoction group. Immunohistochemical staining and Western blot analysis showed that Qiyu Sanlong decoction could up-regulate the expressions of Beclin1, Atg5 and LC3B protein (P<0.01), and promote the conversion from LC3B-Ⅰ into LC3-Ⅱ compared with the model group. Real-time PCR results showed that Qiyu Sanlong decoction could promote the transcription of Beclin1 mRNA and Atg5 mRNA compared with the model group (P<0.01). Conclusion::Qiyu Sanlong decoction has a mild inhibitory effect on lung tumors, and its mechanism may be related to up-regulating the expressions of autophagy key proteins Beclin1, Atg5 and LC3B, and promoting the conversion from LC3B-Ⅰ to LC3B-Ⅱ.

Semaphorin 3A-hypoxia inducible factor 1 subunit alpha co-overexpression enhances the osteogenic differentiation of induced pluripotent stem cells-derived mesenchymal stem cells in vitro / 中华医学杂志(英文版)

BACKGROUND@#Mesenchymal stem or stromal cells (MSCs) derived from the induced pluripotent stem cells (iPSCs) have uniform biological activity, which makes the clinical application of MSCs in bone repair possible. Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration. The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs.@*METHODS@#Sema3A and HIF1α were linked together with the three (GGGGS; G, glycine; S, serine) peptide fragment, and their co-expression in iPSC-MSCs was mediated by a lentiviral vector. The fusion protein retained the immune reactivity for both Sema3A and HIF1α as determined with Western blotting. iPSC-MSCs were infected with overexpression lentivirus (oeLenti) as negative control, oeLenti-Sema3A, oeLenti-HIF1α or oeLenti-Sema3A-HIF1α lentiviruses.@*RESULTS@#Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs (the activity and/or expression of osteoblast markers, such as alkaline phosphatase, osteopontin, and osteocalcin, were upregulated), and suppressed cell survival. The Sema3A-HIF1α fusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival. We further seeded iPSC-MSCs modified by SemaA-HIF1α overexpression onto hydroxyapatite (HA) scaffolds, and evaluated their growth and differentiation on this three-dimensional material. Additional data indicated that, as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes, cells cultured in HA scaffolds grew (blank vs. HA scaffolds: 0.83 vs. 1.39 for survival) and differentiated better (blank vs. HA scaffolds: 11.29 vs. 16.62 for alkaline phosphatase activity).@*CONCLUSION@#Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.

A case report of human thelaziasis and its epidemiology in China / 中国人兽共患病学报

A case of Thelazia callipaeda infection in a 7 months old infant in Dalian was reported.The epidemiology of human thelaziasis in China was investigated in this report.China is the nation with the most reported human Thelazia callipaeda cases in the world,up to 626 case reports of human Thelazia callipaeda infection that were distributed in 28 provinces from 1917 to 2016.We analyzed more than 400 Chinese thelaziosis cases with clinical data from 1917 to 2016.Ages of the patients are from 2 months to 88 years old.Male and female cases are 60.22％ and 39.78％ relatively.The occupation of patients was analyzed,that the preschool children occupied 55.38 ％,farmers occupied 32.27 ％;workers occupied 4.78 ％,and the others occupied the rest 7.57％.This study showed that it is of great significance to strengthen the research on the biology and epidemiology of the sucking nematode,to prevent the spread and epidemic of the disease.

Functional Annotation of Metastasis-associated MicroRNAs of Melanoma: A Meta-analysis of Expression Profiles / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Melanoma is a type of cancer that develops from the pigment-containing cells. Until now, its pathological mechanisms remain largely unknown. The aim of this study was to identify metastasis-related microRNA (miRNAs) and gain an understanding of the biological functions in the metastasis of melanoma.</p><p><b>METHODS</b>We searched the PubMed and Gene Expression Omnibus database to collect miRNA expression profiling datasets about melanoma, with key words of "melanoma", "miRNA", "microarray", and "gene expression profiling". Only the original experimental works published before June 2016 for analyzing the metastasis of melanoma were retained, other nonhuman studies, reviews, and meta-analyses were removed. We performed a meta-analysis to explore the differentially expressed miRNA between metastatic and nonmetastatic samples. Moreover, we predicted target genes of the miRNAs to study their biological roles for these miRNAs.</p><p><b>RESULTS</b>We identified a total of 63 significantly differentially expressed miRNAs by meta-analysis of the melanoma expression profiling data. The regulatory network constructed by using these miRNAs and the predicted targets identified several key genes involved in the metastasis of melanoma. Functional annotation of these genes indicated that they are mainly enriched in some biological pathways such as mitogen-activated protein kinase signaling pathway, cell junction, and focal adhesion.</p><p><b>CONCLUSIONS</b>By collecting the miRNA expression datasets from different platforms, multiple biological markers were identified for the metastasis of melanoma. This study provided novel insights into the molecular mechanisms underlying this disease, thereby aiding the diagnosis and treatment of the disease.</p>

Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 (USP8) gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor (EGFR) signaling and promote adrenocorticotropic hormone (ACTH) production. This study was to investigate whether the inhibition of USP8 activity could be a strategy for the treatment of Cushing's disease (CD).</p><p><b>METHODS</b>The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony formation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition.</p><p><b>RESULTS</b>Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 (ERBB2), and Met leading to a suppression of AtT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis.</p><p><b>CONCLUSIONS</b>Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.</p>

Research progress of traditional mineral Chinese medicine / 中国中药杂志

Traditional mineral Chinese medicine is a characteristic part of Chinese medicine, in the development of traditional Chinese medicine has its unique role. With the development of science and technology and the increase of the medical level, traditional mineral medicine research is gradually thorough and wide-ranging. In recent years, traditional mineral Chinese medicine research mainly includes the physical properties of mineral medicine, structure, chemical composition, pharmacology and treatment mechanism research. The above several aspects of research in the mineral medicine has important practical and theoretical significance. The above several aspects of research status and the problems existing in the research were briefly summarized and reviewed in this paper, and its development were discussed, to provide reference for further studies in the future.

Efficacy and safety of patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the efficacy and safety of patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section.</p><p><b>METHODS</b>A randomized controlled clinical trail was conducted on 180 singleton primiparas (SAS > 30) undergoing selective cesarean section. They were randomly assigned to three groups, i. e., the patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) group (Group A, 60 cases), the patient-controlled sedation with transcutaneous electrical stimulation of auricular eye point group (Group B, 60 cases), and the control group (Group C, 60 cases). Patients in Group A received patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in the operating room. The strength was controlled by patients themselves. The stimulation lasted for 30 min before the epidural puncture till ending the surgery. Patients in Group B received stimulation of auricular eye point. Patients in Group C received pressurization with the same connected line as Group A, but without electric stimulation. The following indices were observed: (1) the bispectral index (BIS), heart rate (HR), mean arterial pressure (MAP), Ramsay sedation score when the women entered the operating room (T0), 30 min after stimulation (T1), at the time after removing the fetus (T2), and by the end of surgery (T3); (2) the concentrations of plasma angiotensin II (AngII) and cortisone (Cor) at the aforesaid time points; (3) the use rates of oxytocin, atropine, and ephedrine; the hemorrhage amount, and the neonatal Apgar score.</p><p><b>RESULTS</b>Compared with Group A, the BIS, the plasma concentrations of AngII and Cor increased at T1, T2, and T3 (P < 0.05), and the Ramsay sedation score decreased (P < 0.05). The HR and MAP increased at T1 (P < 0.05) in Group B and Group C. Compared with T0, the BIS, HR, MAP, and Ramsay sedation score, the plasma concentrations of AnglI and Cor were lowered in Group A at T1 (P < 0.05). There was no statistical difference in the use rates of oxytocin, atropine, and ephedrine; the hemorrhage amount, and the neonatal Apgar score (P > 0.05).</p><p><b>CONCLUSIONS</b>Patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section had obvious sedative effects. It had no adverse effects on puerperal or neonates.</p>

Epigenetic regulation of Wnt signaling pathway gene SRY-related HMG-box 17 in papillary thyroid carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>SRY-related HMG-box 17 (SOX17) encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. Recently, it was considered as a tumor suppressor gene to inhibit canonical Wnt/β-catenin signaling pathway in several malignancies. However, the function of SOX17 in thyroid cancer was unknown. Therefore, we investigated the epigenetic changes and the function of SOX17 in thyroid cancer.</p><p><b>METHODS</b>The methylation status of the promoter region of SOX17 was detected using methylation-specific PCR in 63 papillary thyroid carcinoma (PTC) tissue, 10 normal thyroid tissue, and two thyroid cancer cell lines. Semi-quantitative RT-PCR was used to assess mRNA expression of SOX17 before and after 5-aza-2'-deoxycytidine treatment in thyroid cancer cell lines. Expression of SOX17 and β-catenin were detected by immunohistochemistry in PTC and adjacent tissue. Luciferase reporter assay, colony formation, transfection, and Western blotting were employed to analyze the effect of SOX17 on thyroid cancer cell proliferation and the function of SOX17 in the Wnt signal pathway.</p><p><b>RESULTS</b>Loss of SOX17 expression was correlated to the promoter region hypermethylation in thyroid cancer cell lines. Re-expression of SOX17 was found in TPC-1 cell line after 5-aza-2'-deoxycytidine treatment. In primary thyroid cancer, 60.3% (38/63) were methylated and 39.7% (25/63) unmethylated. But no methylation was found in noncancerous thyroid tissues. Methylation of SOX17 was associated reversely with β-catenin expression in the cytoplasm or nucleus significantly in the PTC (P < 0.05). Colony formation was inhibited by re-expression of SOX17 in TPC-1 cells. SOX17 suppressed the Wnt signaling pathway and the HMG domain was essential for this effect.</p><p><b>CONCLUSIONS</b>SOX17 was frequently methylated in human PTC. Loss of SOX17 expression was induced by promoter region hypermethylation. SOX17 inhibited thyroid cancer proliferation. Methylation of SOX17 activated the Wnt signaling pathway in human thyroid cancer.</p>

Relationship between p53 Arg72Pro polymorphism and cervical carcinoma in Uigur and Han women in Xinjiang / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the association between p53 Arg72Pro polymorphism and cervical carcinomas HPV-associated cervical carcinoma in Uigur and Han women.</p><p><b>METHODS</b>The distribution and frequencies of p53 Arg72Pro genotypes were determined by PCR-RFLP in 152 cases of cervical carcinoma in ethnic Uigur women with 110 cases of normal control and 120 cases of cervical carcinoma in Han women with 122 cases of normal control.</p><p><b>RESULTS</b>The omni-constituent ratio of p53 genotype was statistically different between cervical carcinoma and normal control groups in the Uigur (chi(2) = 7.196, P < 0.05) group. The proportion of Arg/Arg was higher in cervical carcinomas than that in control. The omni-constituent ratio of p53 genotype was statistically different between cervical carcinoma and normal control groups in Han (chi(2) = 8.231, P < 0.025). The proportion of Pro/Pro was higher in cervical carcinoma than that in normal control. The omni-constituent ratio was statistically different between HPV 16 positive and negative groups of cervical carcinoma in the Uigur group (chi(2) = 7.177, P < 0.05). The proportion of Arg/Arg was higher in HPV 16 positive group than that in HPV 16 negative group.</p><p><b>CONCLUSIONS</b>p53 Arg72Pro polymorphism may be associated with the development of cervical carcinoma in Uigur and Han women in Xinjiang. p53 Arg/Arg genotype may be a genetically susceptible factor to HPV-associated cervical carcinoma in Uigur. p53 Pro/Pro genotype may be a genetically susceptible factor to cervical carcinoma in Han. There may be different susceptibilities to cervical cancer between Uigur and Han women in Xinjiang.</p>