CHD1 deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer / 亚洲男科学杂志(英文版)

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.

Effect of Combined Therapy of Lung and Intestine on NF-κB Inflammatory Pathway and Macrophage Polarization in LPS-induced Acute Lung Injury Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of combined therapy of lung and intestine （Mahuangtang + Da Chengqitang） on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in rats and its protective mechanism. MethodWistar rats were randomly divided into blank group， model group， low-， medium-， and high-dose groups with combined therapy of lung and intestine ， and dexamethasone group. LPS （10 mg·kg-1） was given （ip） to induce ALI in rats. The general state of rats in each group was observed and recorded. The body temperature of rats in each group was recorded 0-8 h after modeling by means of anal temperature measurement. Serum and lung tissues were collected 24 h after modeling. Serum levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and arginase-1 （Arg-1） were determined by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the protein levels of nuclear factor kappa B p65 （NF-κB p65）， phosphorylated NF-κB p65 （p-NF-κB p65）， NF-κB inhibitor α （IκBα）， and phosphorylated IκBα （p-IκBα） in lung tissues of rats. The levels of classically activated （M1） macrophage marker CD80 and IL-1β and macrophage markers F4/80 and IL-10 were detected by double immunofluorescence. ResultCompared with the blank group， the model group showed increased body temperature and thermal response index （TRI）， elevated serum levels of pro-inflammatory factor TNF-α and IL-1β and anti-inflammatory factor IL-10 （P<0.01）， up-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues （P<0.01）， and increased levels of F4/80， CD80， and IL-1β in lung tissues （P<0.01）. Compared with the model group， the lung-intestine combined treatment groups and the dexamethasone group exhibited decreased body temperature and TRI in rats （P<0.01）， declined serum levels of inflammatory factor TNF-α and IL-1β （P<0.05， P<0.01）， elevated serum levels of anti-inflammatory factor IL-10 and Arg-1 （P<0.05， P<0.01）， down-regulated protein levels of p-NF-κB p65 and p-IκBα in lung tissues （P<0.05， P<0.01）， decreased levels of CD80 and IL-1β， and increased levels of IL-10 in lung tissues （P<0.01）， while the level of F4/80 was not significantly changed. ConclusionThe combined therapy of lung and intestine can obviously alleviate the fever and inflammatory state of ALI rats， and the mechanism may be related to the inhibition of NF-κB inflammatory pathway and the polarization of lung tissue macrophages to anti-inflammatory phenotype.

Current Status of Hyperbaric Oxygen Therapy and Its Application / 中国医疗器械杂志

Hyperbaric oxygen therapy is a method of breathing pure oxygen or high-concentration oxygen in a highpressure environment to treat hypoxic diseases and related diseases. According to clinical verification, this therapy has an irreplaceable effect on certain diseases and has gradually become a comprehensive clinical treatment. One of the main methods of certain diseases is widely recognized by the medical field at home and abroad. The development history, treatment principles, key technologies, and future development trends of hyperbaric oxygen are discussed in detail, provide a research direction for the development of hyperbaric oxygen therapy in the future, and at the same time, it has also improved physicians' awareness of hyperbaric oxygen therapy, so as to improving Industry influence.

Mechanism of lung and intestine combination therapy in treatment of acute lung injury by inhibiting inflammatory response based on NF-κB/NLRP3 signaling pathway and alveolar macrophage activation / 中国中药杂志

Lung and intestine combination therapy(LICT) is effective in the treatment of acute lung injury(ALI). In this study, the combination of Mahuang Decoction and Dachengqi Decoction(hereinafter referred to as the combination), a manifestation of LICT, was employed to explore the effect of nuclear factor kappaB(NF-κB)/nucleotide binding oligomerization domain-like receptors-3(NLRP3) pathway and alveolar macrophage activation on the lung inflammation in rats with ALI, for the purpose of elucidating the mechanism of LICT in treating ALI. After the modeling of ALI with limpolysaccharide(LPS, ip), rats were respectively given(ig) the combination at 10, 7.5, and 5 g·kg~(-1)(high-dose, medium-dose, and low-dose LICT groups, separately), once every 8 h for 3 times. Haematoxylin-eosin(HE) staining was used to observe the histopathological changes of lung tissue, followed by the scoring of inflammation. Immunohistochemistry was applied to detect alveolar macrophage activation, enzyme-linked immunosorbent assay(ELISA) was applied to detect the serum content of tumor necrosis factor-α(TNF-α) and interleukin-18(IL-18), Western blot was applied to detect the protein expression of phosphorylated-nuclear factor kappaB p65(p-NF-κB p65), nuclear factor kappaB p65(NF-κB p65), phosphorylated-inhibitor kappaB alpha(p-IκBα), inhibitor kappaB alpha(IκBα), and NLRP3 in lung tissue, and quantitative reverse transcription-PCR(qRT-PCR) was applied to detect the mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. The results showed that LICT groups demonstrated lung injury relief, decrease in inflammation score, alleviation of alveolar macrophage activation, significant decline in serum content of inflammatory factors TNF-α and IL-18, and decrease of the protein expression of p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3, and mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. In summary, LICT has definite therapeutic effect on ALI. The mechanism is that it inhibits alveolar macrophage activation by suppressing NF-κB/NLRP3 signaling pathway, thereby reducing the activation and release of inflammatory factors and finally inhibiting inflammation.

MicroRNA expression profile in the process of cyclic mechanical stretch promoting C2C12 myogenesis / 中国组织工程研究

BACKGROUND:In recent years,the incidence of skeletal muscle injury becomes higher and higher,but the skeletal muscle repair ability is limited;therefore,studies on the molecular mechanism of skeletal muscle repair play a positive role in the treatment of skeletal muscle injury.OBJECTIVE:To explore the role of microRNA in skeletal muscle regeneration.METHODS:C2C12 myoblasts were cyclic stretched in vitro by the Flexercell-5000 flexible device,and the appropriate stretch condition which could induce myogenesis was selected.The microRNA expression alteration during mechanical stretch-induced myoblast myogenesis was explored using high-throughout sequencing,and the differentially expressed microRNAs were further studied by the bioinformatics analysis.RESULTS AND CONCLUSION:10％ deformation,0.125 Hz cyclic mechanical stretch could promote myoblast proliferation and increase MyoD and Myogenin expressions in C2C12 myoblasts.MicroRNA expression profile alteration,including the downregulated miR-500-3p/1934-5p/31-3p/378a-5p/3473b/331-3p/5097 and upregulated miR-340-5p/449c-Sp/1941-3p,were all involved in the stretch-mediated myoblast myogenesis,and the MAPK signal pathway seemed to participate in this process.These results suggest that the low frequency of the cyclic mechanical stretch can upregulate the expression levels of myogenic regulatory factors through the alteration of MicroRNA expression,further inducing myogenesis,which the MAPK signal pathway may be involved in.

Postoperative analgesia of Ropivacaine combined Dexmedetomidine for transversus abdominis plane block in laparoscopic surgery / 中国内镜杂志

Objective To observe the effect of postoperative analgesia of Ropivacaine combined Dexmedetomidine for transversus abdominis plane (TAP) block in laparoscopic surgery. Methods 60 patients underwent selective laparoscopic hernia repair were randomly divided into two groups: Ropivacine plus Dexmedetomidine group (Rpd group): Dexmedetomidine 1.0 μg/kg + 0.4% Ropivacine 30 ml was injected into bilateral TAP, and Ropivacine group (R group): saline 1 ml+0.4% Ropivacine 30 ml was injected into bilateral TAP. Blood pressure and heart rate on beginning of the surgery, 1 h during surgery and leaving the operating room, VAS of immediate postoperative period, 4 h, 6 h, 8 h, 12 h, 24 h after the surgery, analgesic duration and incidence of nausea and vomiting of the two groups were recorded. Results Two groups have no difference in blood pressure and heart rate in all time points (P > 0.05), VAS score of 6 h, 8 h, 12 h after surgery in Rpd group were lower than in R group (P < 0.05), and VAS score of postoperative period, 4 h, 24 h after the surgery had no difference between the two groups (P > 0.05). Sensory block duration in Rpd group was longer than in R group (P < 0.05). Incidence of nausea and vomiting of the two groups had no difference in two groups (P > 0.05). Conclusions Ropivacaine combined Dexmedetomidine for Transversus Abdominis Plane block in laparoscopy patients can significantly prolong the analgesic duration.

Postoperative analgesia of Ropivacaine combined Dexmedetomidine for transversus abdominis plane block in laparoscopic surgery / 中国内镜杂志

Objective To observe the effect of postoperative analgesia of Ropivacaine combined Dexmedetomidine for transversus abdominis plane (TAP) block in laparoscopic surgery. Methods 60 patients underwent selective laparoscopic hernia repair were randomly divided into two groups: Ropivacine plus Dexmedetomidine group (Rpd group): Dexmedetomidine 1.0 μg/kg + 0.4% Ropivacine 30 ml was injected into bilateral TAP, and Ropivacine group (R group): saline 1 ml+0.4% Ropivacine 30 ml was injected into bilateral TAP. Blood pressure and heart rate on beginning of the surgery, 1 h during surgery and leaving the operating room, VAS of immediate postoperative period, 4 h, 6 h, 8 h, 12 h, 24 h after the surgery, analgesic duration and incidence of nausea and vomiting of the two groups were recorded. Results Two groups have no difference in blood pressure and heart rate in all time points (P > 0.05), VAS score of 6 h, 8 h, 12 h after surgery in Rpd group were lower than in R group (P < 0.05), and VAS score of postoperative period, 4 h, 24 h after the surgery had no difference between the two groups (P > 0.05). Sensory block duration in Rpd group was longer than in R group (P < 0.05). Incidence of nausea and vomiting of the two groups had no difference in two groups (P > 0.05). Conclusions Ropivacaine combined Dexmedetomidine for Transversus Abdominis Plane block in laparoscopy patients can significantly prolong the analgesic duration.

An ultrasonographic study of the correlation between developmental dysplasia of the hip and congenital muscular torticollis in children / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the significance of early screening of pediatric developmental dysplasia of the hip (DDH) and congenital muscular torticollis (CMT) using ultrasonography and establish a simultaneous screening model for pediatric DDH and CMT.</p><p><b>METHODS</b>From January, 2013 to January, 2016, a total of 5060 pediatric patients with suspected DDH and CMT underwent ultrasonic examinations. The diagnostic results of the two diseases were classified into different clinical types, and Chi-square test was used to analyze the one-way relationship between different types of DDH and CMT; correspondence analysis was used for multivariate analysis of the variables. Chi-square test was used to analyze the difference between the detection rates in suspected CMT patients and the normal population.</p><p><b>RESULTS</b>GrafIIa type DDH was associated with mass-type CMT in the children (χ=331.800, P<0.001). DDH of GrafIIb, GrafIIc, Graf III, and Graf IV types were related with non-tumor type of CMT. The children with a suspected diagnosis of CMT showed a significantly higher detection rate of DDH than the normal subjects (χ=321.889, P<0.001).</p><p><b>CONCLUSION</b>DDH is closely related with CMT. Early simultaneous screening of DDH and CMT can help to improve the early diagnosis rate of CMT in children.</p>

Determination of Gallic Acid,Quercetin and Kaempferol in Gongyanping Capsules by HPLC / 中国药师

Objective:To establish an HPLC method for the determination of gallic acid,quercetin and kaempferol in Gongyanping capsules. Methods:HPLC was applied with the chromatographic conditions as follows: The chromatographic column was Agilent-SB C18 (250 mm × 4. 6 mm,5 μm) at 30℃; the mobile phrase was methanol-0. 3% phosphoric acid solution with gradient elution; the flow rate was 1. 0 ml·min-1. Results: The linearity relationship of gallic acid, quercetin and kaempferol was within the range of 98.200-491.00 μg·ml-1(r=0.999 9), 7.520-37.600 μg·ml-1(r=0.999 9) and 4.940-24.700 μg·ml-1(r=0.999 9), re-spectively;the average recovery was 96. 74%(RSD=1. 33%), 98. 18%(RSD=1. 70%) and 97. 04%(RSD=1. 28%),respective-ly. Conclusion:The method is simple, accurate and repeatable.

Epithelial-mesenchymal transition and human fetal prostate development / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the role and significance of epithelial-mesenchymal transition (EMT) and its transcriptional regulator Twist1 in the development of the human fetal prostate.</p><p><b>METHODS</b>Twenty-five human fetal prostate specimens at various developmental stages (16-39 weeks) were included in this study. EMT markers, such as E-Cadherin, N-Cadherin and Vimentin, and EMT transcriptional regulator Twist1 were determined by immunohistochemistry, and their relationship with the development of the human fetal prostate was analyzed.</p><p><b>RESULTS</b>E-Cadherin was expressed in the fetal prostate epithelium only, while Vimentin, N-Cadherin and Twist1 in both the epithelium and the stroma. The expression of E-Cadherin gradually increased, but those of Vimentin, N-Cadherin and Twist1 gradually decreased with the gestation stages. No significant changes were observed in the staining patterns of Vimentin, N-Cadherin and Twist1 in the stroma during the whole developmental process.</p><p><b>CONCLUSION</b>EMT is involved in the development of the human fetal prostate, which may promote epithelial cell motility to form prostatic bud tubules in early gestation stages and boost the differentiation of prostate epithelia in later stages.</p>

Comparison of transcription factors repressing epithelial phenotype in two different prostate cancer EMT models and its significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To screen and compare the specific transcription factors that repress the epithelial phenotype in epithelial-mesenchymal transition (EMT) in two different human prostate cancer models LNCaP/HIF1alpha and ARCaP.</p><p><b>METHODS</b>We established two different prostate cancer EMT models, LNCaP/HIF1alpha and ARCaP, cultured LNCaP, LNCaP/HIF1alpha, IF11 and IA8 cells in vitro, and detected the five transcription factors Snail, Slug, ZEB1, SIP1 and Twist1 in these cells by RT-PCR.</p><p><b>RESULTS</b>Different levels of Snail, Slug, ZEB1, SIP1 and Twist1 were detected in both LNCaP and LNCaP/HIF1alpha cells, with significant differences only in the expressions of Slug and Twist1 between the two cells. The expression of Slug was increased, but that of Twist1 decreased in the LNCaP/HIF1alpha cells. All the five transcription factors but Twist1 were expressed in both the IF11 and IA8 cells, but only the express- sions of ZEB1 and Slug were increased significantly in the IA8 cells.</p><p><b>CONCLUSION</b>There are different mechanisms underlying transcriptional regulation in different prostate cancer EMT models. Slug may be one of the key transcription factors involved in the HIF1alpha-induced EMT of LNCaP cells, while ZEB1 and Slug may play an important role in repressing the epithelial phenotype of the ARCaP model.</p>