Distant organ metastasis patterns and prognosis of cervical adenocarcinoma: a population-based retrospective study.

Background: Adenocarcinoma is a common histological subtype of cervical cancer, accounting for 10-15% of all cases. The prognosis of cervical adenocarcinoma with distant organ metastases remains unclear. Therefore, our study aimed to investigate the patterns and prognosis of distant organ metastasis in cervical adenocarcinoma. Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2019. Cox regression, Kaplan-Meier, and log-rank analyses were conducted. Results: We observed that adenocarcinoma (AC) of the cervix primarily metastasizes to single organs, with a rate of 73.3%. The lungs are the most common organs of metastasis, followed by the liver and bones. Patients with bone metastases have a median survival period of 12 months, which is slightly longer compared to metastasis in other organs. Distant organ metastasis, age, positive lymph nodes, higher AJCC stages, larger tumor diameter, and higher cell grades are related to poor prognosis (p < 0.001). Furthermore, we have observed that surgical intervention, radiotherapy, and chemotherapy can potentially provide benefits for patients with distant organ metastases. Conclusion: Metastasis is an independent prognostic factor for cervical adenocarcinoma patients. Surgery, radiotherapy, and chemotherapy can provide an overall survival advantage for patients with distant organ metastases.

Misdiagnosis of scalp angiosarcoma: A case report.

BACKGROUND: Angiosarcoma is a rare malignant tumor. Owing to the lack of specific clinical manifestations of this disease, it is difficult to achieve early diagnosis and start early treatment. CASE SUMMARY: A 78-year-old male patient was admitted to the hospital because of a bump on his head that did not heal for 4 mo. The patient was diagnosed with a refractory head wound. The patient underwent neoplasm resection and skin grafting surgery in the Plastic Surgery. The neoplasm was sent for pathological examination during the operation. The final pathological results were confirmed scalp angiosarcoma. CONCLUSION: Our research suggests that pathological examination should be performed for refractory ulcers of the scalp, and physical factor therapy should be used with caution before the diagnosis is clear.

ALKBH5 inhibits the SIRT3/ACC1 axis to regulate fatty acid metabolism via an m6A-IGF2BP1-dependent manner in cervical squamous cell carcinoma.

Cervical cancer (CC) is the most common malignancy of the female reproductive system, among which cervical squamous cell carcinoma (CESC) is the most common type. The demethylase ALKBH5 has been previously revealed to be downregulated in CC tissue. N6 methyladenine (m6A) is the most common modification in eukaryotic RNAs and is involved in modulating tumour progression. Therefore, we attempted to clarify the ALKBH5 role and mechanism underlying CESC progression. In CESC, patient tissue and control tissue m6A levels were measured. Reverse transcription quantitative real-time polymerase chain reaction, western blotting and immunochemistry were used to measure ALKBH5 levels. A correlation between CESC patient survival and ALKBH5 levels was evaluated. Wound healing, transwell and colony formation assays were used to detect CESC cellular behaviours. Corresponding kits and BODIPY staining were used to detect CESC lipid metabolism. Bioinformatics, immunoprecipitation, RNA pulldown and RNA immunoprecipitation assays as well as half-life measurements were used to assess the association and mechanism of ALKBH5 with silent mating type information regulation 2 homologue 3 (SIRT3), acetyl-CoA carboxylase 1 (ACC1) and insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1). The m6A demethylase ALKBH5 was depleted in CESC tissue and cells, and a low level of ALKBH5 predicted an unfavourable prognosis in CESC patients. ALKBH5 overexpression suppressed CESC growth and lipid metabolism in vitro and CESC tumour growth in vivo, and ACC1 overexpression rescued these changes. ALKBH5 downregulated ACC1 levels in CESC cells by facilitating SIRT3 methylation to repress ACC1 deacetylation. ALKBH5 destabilized SIRT3 to downregulate SIRT3 levels in CESCs in an m6A-IGF2BP1-dependent manner. ALKBH5 demethylates and destabilizes SIRT3 in an m6A-IGF2BP1-dependent manner, repressing CESC growth, lipid metabolism and tumorigenesis by downregulating ACC1.

Key Prediction Genes of Nasopharyngeal Carcinoma:Screening Based on Systematic Bioinformatics and Validation by Cell Experiments / 中国医学科学院学报

Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.

Exosomal miR-543 Inhibits the Proliferation of Ovarian Cancer by Targeting IGF2.

Objective: Ovarian cancer (OvCa) is the most lethal gynaecological malignancy worldwide. We aimed to illustrate the potential function and molecular mechanism of exosomal microRNA-543 (miR-543) in the oncogenesis and development of OvCa. Methods: Differentially expressed microRNAs in exosomes derived from OvCa cell lines were identified by bioinformatic analysis and verified by RT-PCR. Cell proliferation ability was estimated by clonogenic and 5-ethynyl-2'-deoxyuridine assays in vitro and in vivo. Potential involved pathways and targets of exosomal miRNAs were analysed using DIANA and verified by pyrosequencing, glucose quantification, dual-luciferase reporter experiments, and functional rescue assays. Results: Bioinformatic analysis identified miR-543 and its potential target genes involved in the cancer-associated proteoglycan pathway. The expression of miR-543 was significantly decreased in exosomes derived from OvCa cell lines, patient serum, and OvCa tissues, while the mRNA levels of insulin-like growth factor 2 (IGF2) were increased. Furthermore, the overexpression of miR-543 resulted in the suppression of OvCa cell proliferation in vitro and in vivo. Moreover, miR-543 was significantly negatively correlated with IGF2 in OvCa tissues in comparison with paracarcinoma tissues. Notably, upregulation of miR-543 led to increased cell supernatant glucose levels and suppressed cell growth, which was rescued by overexpression of IGF2. Conclusions: Exosomal miR-543 participates in the proteoglycan pathway to suppress cell proliferation by targeting IGF2 in OvCa.

Comparison of prognosis of patients with endometrial cancer after hysteroscopy versus dilatation and curettage: A multicenter retrospective study.

Introduction: Hysteroscopy is a useful procedure for diagnosing endometrial cancer. There is controversy regarding whether hysteroscopy affects the prognosis of endometrial cancer by prompting cancer cell into intraperitoneal dissemination. Our purpose was to confirm whether hysteroscopy could be a risk factor of the tumor stage, recurrence and survival rate of endometrial cancer. Methods: This multicenter retrospective study included all consecutive patients who had endometrial carcinoma diagnosed preoperatively with hysteroscopy and directed endometrial biopsy (HSC, group A) and dilatation and curettage (D&C, group B) between February 2014 and December 2018 at the Fujian Provincial, China. We compared the demographic feature, clinical characteristics and prognosis between the two groups. Results: A total of 429 patients were included in the study (Group A, n = 77; Group B, n = 352). There was no significant difference between their baseline characteristics [including age, BMI, histological type and International Federation of Gynecology and Obstetrics (FIGO) stage]. By comparing several pathological conditions that may affect prognosis, there were no significant differences between the two groups in the peritoneal cytology, depth of myometrial invasion, the positivity of lymph nodes, lymphovascular space invasion and paraaortic lymph node dissection. Finally, no significant difference was found between the two groups in overall survival (OS) (P = 0.189) or recurrence free survival (RFS) (P = 0.787). Conclusion: Under certain inflation pressure and distension medium, hysteroscopic examination and lesion biopsy ensure the safety and have no adverse effects on prognosis compared to conventional curettage.

[Evaluation of the effect of Er:YAG laser combined with guided bone regeneration in the treatment of peri-implantitis with osseous defects].

PURPOSE: To evaluate the clinical benefits of Er:YAG laser combined with guided bone regeneration (GBR) in the treatment of peri-implantitis-assocaited osseous defects. METHODS: Twenty-six patients (34 implants in total) who underwent implant restoration in Dental Disease Prevention and Treatment Institute, Jiading District, from 2017 to 2019 and were diagnosed with peri-implantitis with osseous defects, and randomly divided into the experimental group and control group. The two groups of patients received open flap surgery, debridement and GBR treatment. The only difference in the experimental group was the use of Er: YAG laser to modulate and remove inflammatory tissue as well as to decontaminate the implant surface, instead of traditional mechanical treatment in the control group. The probing depth (PD), bleeding on probing (BOP), and plaque index (PI), the height of the bone defect around the implant (reduce of marginal bone level, RBL) were recorded and compared. SPSS 20.0 software package was used to analyze the data. RESULTS: The PD, BOP, PI and RBL of the two groups of patients were significantly improved after treatment with different methods. There was no significant difference in the improvement of PD, BOP and PI between the two groups 6, 12 and 24 months after treatment, while the improvement of RBL in the experimental group was significantly better than that of the control group 12 and 24 months after treatment. CONCLUSIONS: In the treatment of GBR with peri-implantitis and osseous defects, Er: YAG laser therapy is more effective than traditional mechanical methods, and is more conducive to the regeneration of new bone.

Composition characteristics of the gut microbiota in infants and young children of under 6 years old between Beijing and Japan.

BACKGROUND: The composition of intestinal flora in Chinese and Japanese has been reported in many studies but that in infants aged 0-6 years old has not been studied yet. METHODS: The distribution characteristics of the fecal flora of infants in Beijing (n=84) and Japan (n=53) were analyzed using 16S rRNA gene sequencing analysis. RESULTS: This study showed the higher relative abundance of Erysipelotrichaceae_ UCG-003 and Anaerostipes in male group that of Ruminiclostridium, Eubacterium, Senegalimassilia and Senegalimassilia in female group, especially Senegalimassilia, which was not detected in male group. Defecation trait groups indicated significantly higher relative abundance of Bifidobacterium in abnormal bowel trait group than that in the normal group (P<0.05). The feeding groups' analysis showed significantly higher relative abundance of Bifidobacterium and Enterococcus and lower abundance of Bacteroides and Lacetospirillaceae in the breast-feeding group than that in the formula feeding and mixed-feeding groups. The relative abundance of Parasutterella and Ruminococcaceae_UCG-003 in the halitosis group was significantly higher than that in the normal group. The comparison of cold and fever group and normal group indicated significantly higher relative abundance of Erysipelatoclostridium and lower relative abundance of Lachnospiraceae _UCG-001 in the fever and cold group than that in the normal group (P<0.05). The regional comparison of intestinal flora of Beijing and Japan showed significant increase in the relative abundance of Bacillus, Lactobacillus, Prevotella, megamonas and Veillonella in the intestinal flora of 0-6 years old infants in Beijing. CONCLUSIONS: These findings improve the understanding of intestinal bacterial and viral communities of infants from the two Asian countries.

Toxicity reduction and water expelling effect preservation of Shizaotang after its toxic members processing with vinegar on rats with malignant pleural effusions.

ETHNOPHARMACOLOGICAL RELEVANCE: Shizaotang (SZT), consisted of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), Euphorbia pekinensis Rupr. (EP), Daphne genkwa Sieb. et Zucc. (DG，fried) and Ziziphus jujuba Mill. (ZJ), is usually used for treating malignant pleural effusions (MPE), but the toxicity of EK and EP limits its clinical safe application. It was reported that vinegar processing can reduce the toxicity of EK and EP. Whether EK and EP processing with vinegar can cause the reduced toxicity and retained pharmacological effects of SZT, it still remains unknown. AIM OF THE STUDY: We aimed to evaluate whether using vinegar processed EK and EP would reduce toxicity and preserve water expelling effect of SZT. MATERIALS AND METHODS: Network pharmacology and qualitative analysis of SZT/VSZT were used to construct compound-target-pathway network of their effects and toxicity. Pleural fluid weight, urine volume, uric electrolyte, pH, pro-inflammatory cytokines in pleural fluid, serum Renin-Angiotensin-Aldosterone System (RAAS), anti-diuretic hormone (ADH) and intestinal aquaporin 8 (AQP8) protein were used to evaluate the effect mechanisms involved in rats experiments. And liver damage, oxidative damage and HE staining (liver, stomach, and intestine) were used to determine the toxicity. RESULTS: Network pharmacology analysis reviewed inflammation-related pathways of the effect and toxicity of SZT/VSZT: VEGF-PI3K-AKT pathway inhibited MPE by changing the vasopermeability; PI3K-Akt/Mitogen-activated protein kinase (MAPK)/TNF-NF-κB signaling pathway inhibited MPE by up-regulating expression of AQP8 protein. In vivo experiments displayed that SZT/VSZT could reduce pleural fluid, increase urine volume, lower pro-inflammatory cytokines levels and up-regulate AQP8 protein expression significantly (P < 0.05, P < 0.01). In addition, disorders on electrolyte (Na+, K+ and Cl-) and pH were ameliorated (P < 0.05, P < 0.01). The levels of RAAS and ADH were significantly dose-dependently called back (P < 0.01). These findings were partly consistent with the results of network pharmacology analysis. Results of toxicity experiments demonstrated that SZT and VSZT exhibited certain toxicity on normal rats, and VSZT had lower toxicity than that of SZT. Interestingly, SZT and VSZT exerted alleviation effect to the liver damage and oxidative damage on model rats. CONCLUSION: SZT/VSZT improved MPE by regulating associated inflammation pathways. Besides, compared to SZT, VSZT showed lower toxicity and equivalent expelling MPE effect. This study may provide scientific basis for guiding the clinical application of SZT.

Anatomical distribution of lower-extremity deep venous thrombosis in patients with acute stroke.

OBJECTIVE: Post-stroke paralysis is a common contributor to deep vein thrombosis (DVT) of the lower extremities, but little is known about its epidemiology and anatomy. This prospective study aimed to investigate the clinical incidence and anatomical distribution of lower-extremity DVT in acute stroke. PATIENTS AND METHODS: A total of 679 patients diagnosed with acute stroke (ischemic stroke, n = 507; hemorrhagic stroke, n = 172) were enrolled. Lower-extremity DVT was evaluated using vascular ultrasonography, and classified into three subtypes: central type, peripheral type and mixed type. Then, the incidence and anatomical distribution of DVT were analyzed. RESULTS: For patients with ischemic stroke, a total of 107 patients (21.1%) were affected by DVT, and 119 extremities were found with DVT, which included 114 extremities with peripheral-type DVT and five extremities with mixed-type DVT. For patients with hemorrhagic stroke, a total of 49 patients (28.5%) were affected by DVT, and 55 extremities were found with DVT, which included 51 extremities with peripheral-type DVT and four extremities with mixed-type DVT. The incidence of DVT was significantly higher in patients with hemorrhagic stroke than in patients with ischemic stroke (P < 0.05). Intermuscular veins were the most commonly affected (96.6%), followed by peroneal veins (15.5%), posterior tibial veins (9.2%), popliteal veins (4.0%), and femoral veins (4.0%). There was no significant difference in the anatomical distribution of DVT between ischemic and hemorrhagic stroke (P > 0.05). CONCLUSION: DVT is a common complication of acute stroke, and hemorrhagic stroke is associated with a higher incidence of DVT. The anatomical distribution of DVT revealed no heterogeneity between ischemic and hemorrhagic stroke, and isolated DVT in intermuscular veins were the most common.

Effect of the vinegar-process on chemical compositions and biological activities of Euphorbia kansui: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) the root of Euphorbia kansui S.L.Liou ex S.B.Ho (EK), is used for treating edema and ascites but is also of toxicological concerns. And the clinical applications of EK have been seriously restricted for its severe toxicity. To reduce its toxicity, a commonly used clinical practice is processing it with vinegar. AIM OF THE REVIEW: This review aimed to summarize and discuss updated information on biological activities and phytochemistry of EK before and after vinegar-processing, and provide feasible insights for further research on the chemical composition, toxicity and pharmacological effects of EK before and after vinegar-processing. MATERIALS AND METHODS: The relevant information on chemical compositions and biological activities of EK before and after vinegar-processing was collected from scientific databases (Google Scholar, PubMed, CNKI, SpringerLink, Web of Science, Wiley Online Library and SciFinder). Additionally, published and unpublished Ph.D. and MSc. dissertations were also obtained from online databases. RESULTS AND DISCUSSIONS: Diuretic and purgative effect of EK are well documented pharmacologically as are acute, irritant and organic toxic effects. Some of about terpenoids reported have antiproliferative effects on cancer cells and potential antiviral effect. After processing with vinegar, the contents of terpenoids mostly were reduced (ingenane and jatrophane type) with some new compounds being generated (unclear). Also, the toxicity of EK was decreased (using mice, rats and zebrafish embryos model), while the diuretic and purgative effects were retained (using cancerous ascites model rats and mice). CONCLUSIONS: While some evidence exists for the reduction of toxicity without compromising the pharmacological effects of EK after vinegar processing, the specific mechanism of action remains unknown. Consequently, further research is necessary to investigate the mechanisms and the relationship between vinegar processing and changes in the chemical composition as well as pharmacological effects/toxicity. This is essential before a safe clinical use can be endorsed.

Determination of kansuiphorin C and kansuinin A in rat feces using UFLC-MS/MS and its application in the comparative excretion study on normal and malignant ascites rats.

Malignant ascites (MA) is one of the severe complications of gastrointestinal tumors, affecting the patients' survival time and quality of life. Euphorbia kansui is a commonly used toxic Chinese herbal medicine for malignant ascites. Our previous study showed that the biological and toxicological effects of kansui were closely related to the gastrointestinal tract. The ingenane-type and jastrophane-type diterpenoids are both toxic and active components of kansui. The contents of kansuiphorin C (KPC) and kansuinin A (KA) take highest accounts in each type of diterpene. Hence, in this study, the efficacy and toxicity of KPC and KA on normal rats and MA rats were firstly evaluated by serum liver enzymes (ALT and AST), oxidative damage indicators (GSH, SOD, MDA and LDH), inflammatory indexes (TNF-α, IFN-γ and IL-2) and the volume of ascites. Changes in the levels of these indices showed that although the toxicity of KPC on normal rats was stronger than KA, KPC exhibited better efficacy to the malignant ascites with no obvious side effects at the dose of 10 mg·kg-1. Then, accurate and reliable methods for the determination of KPC and KA in the rat feces by ultra-fast liquid chromatography coupled with MS/MS detector (UFLC-MS/MS) were established, detected by the multiple reaction monitoring mode. The chromatographic separation was conducted on an XBbridge C18 column (50 mm × 2.1 mm, 2.5 µm) using gradient elution composed of 0.1% formic acid in water and acetonitrile. The flow rate was 0.5 mL·min-1 and column temperature was 30 °C. The method was finally applied to the comparative study on normal and malignant ascites rats given KPC and KA, respectively. Interestingly, the results showed that KPC's accumulative fecal excretion rate (normal, 19.22%±5.36%; model, 15.96%±3.47%) were much higher than that of KA (normal, 2.928%±0.741%; model, 2.835%±0.873%) at the same dose within 48 h. This suggested KPC had higher in-vivo transformations in comparison with KA, providing guidance for the further preclinical research of KPC and KA as promising compounds treating MA.

Acute Toxicity of Shizaotang in Rats / 中国实验方剂学杂志

Objective:To study the acute toxicity of Shizaotang in rats, in order to provide reference for clinical drug safety and subsequent toxicological efficacy experiments. Method:Totally 40 SPF SD rats were randomly divided into control group and Shizaotang group, with 20 rats in each group (10 males and 10 females). By the maximum dose method, the Shizaotang group was given the maximum concentration of Shizaotang suspension 0.3 g·mL-1 for 2 consecutive times in the maximum dosage volume within 24 h, and the control group was given normal saline. The toxicity (death, poisoning symptoms) and its severity and recovery of the rats were observed within 14 days, and the changes in body weight and feeding before and after administration were recorded. After 14 days, the rats were put to death, and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), creatinine (SCr), and interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α) and nuclear factor-κB (NF-κB) levels were measured, each tissue was weighed, and organ coefficients were calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of various organs, and evaluate the acute toxicity. Result:No animal death, obvious poisoning symptom, and visible organ abnormality were observed. Compared with the control group, there was no significant change in body weight and food consumption in the drug-administered group. There was no significant difference in the organ coefficients of rats. Serum ALT, AST, BUN, SCr, IL-2, TNF-α, and NF-κB did not change significantly, and no abnormality was observed in pathological sections of each tissue. Conclusion:The maximum oral dosage of Shizaotang in rats is 12 g·kg-1, which is 480 times of daily dosage for adults, with a good safety. This suggests that Shizaotang has a certain safety range.

Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF-β1/Smad pathway / 中国天然药物

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.

Taxus chinensis ameliorates diabetic nephropathy through down-regulating TGF-β1/Smad pathway / 中国天然药物

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.

Downregulation of miR-214-3p May Contribute to Pathogenesis of Ulcerative Colitis via Targeting STAT6.

MicroRNAs (miRs) are small noncoding RNA molecules and recently have demonstrated that altered expression and functions are their tight association with ulcerative colitis (UC). Previous microarray study reported that miR-214 was downregulated in the sigmoid colon of patients with active UC, but the roles of miR-214 in the pathogenesis of UC remain to be elucidated. In this study, significant lower level of miR-214-3p and higher level of STAT6 in the intestinal mucosa of active UC patients compared with the health controls were confirmed by quantitative real-time PCR. Results of luciferase reporter assays and western blot demonstrated that miR-214-3p directly targets STAT6 and negatively regulates the expression of STAT6 at the posttranscriptional level. Furthermore, the expression of miR-214-3p was decreased in TNF-α treated HT29 cells and STAT6 protein level was increased in a time-dependent manner. Silenced STAT6 and upregulation of miR-214-3p could decrease the level of INF-γ in TNF-α treated HT29 cells. Additionally, the results of the present study indicate that miR-214-3p and STAT6 axis may be a novel therapeutic target for intestinal inflammation of patients with active UC.

Nephroprotective Effects of Anthocyanin from the Fruits of Panax ginseng (GFA) on Cisplatin-Induced Acute Kidney Injury in Mice.

Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin. The formation of kidney malondialdehyde, heme oxygenase-1, cytochrome P450 E1 and 4-hydroxynonenal with a concomitant reduction in reduced glutathione was also inhibited by GFA, while the activities of kidney superoxide dismutase and catalase were all increased. GFA also inhibited the increase in serum tumour necrosis factor-α and interleukin-1ß induced by cisplatin. In addition, the levels of induced nitric oxide synthase and cyclooxygenase-2 were suppressed by GFA. Furthermore, GFA supplementation inhibited the activation of apoptotic pathways by increasing B cell lymphoma 2 and decreasing Bcl2-associated X protein expression. In conclusion, the findings from the present investigation demonstrate that GFA pre-administration can significantly prevent cisplatin-induced nephrotoxicity, which may be related to its antioxidant, anti-apoptotic and antiinflammatory effects. Copyright © 2017 John Wiley & Sons, Ltd.

Association of VEGF and VDR gene- gene and gene- smoking interaction on risk of multiple myeloma in Chinese Han population.

AIMS: To investigate the association of several single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) and vitamin D receptor (VDR) gene polymorphisms and additional gene- gene and gene- smoking interaction with multiple myeloma (MM) risk in Chinese population. METHODS: Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association between 6 SNPs within VEGF and VDR gene, additional gene- gene and gene- smoking interaction on MM risk. RESULTS: MM risk is significantly higher in carriers with the rs699947- A allele within VEGF gene than those with CC genotype (CA+ AA versus CC), adjusted OR (95%CI) =1.72 (1.19-2.33), and higher in carriers with rs2228570- T allele within VDR gene than those with CC genotype (CT+ TT versus CC), adjusted OR (95%CI) = 1.68 (1.26-2.17). We also found a significant two-locus model (p=0.0010) involving rs699947 and rs2228570, and a significant two-locus model (p=0.0107) involving rs2228570 andsmoking. Participants with rs699947- CA+AA and rs2228570- CT+TT genotype had the highest MM risk, compared to participants with rs699947- CC and rs2228570- CC genotype, OR (95%CI) = 3.12 (1.82 -4.61). Smokers with rs2228570- CT+TT genotype had the highest MM risk, compared to never- smokers with rs2228570- CC genotype, OR (95%CI) = 3.27 (1.74-4.86). CONCLUSIONS: We found that the A allele of rs699947 within VEGF and T allele of rs2228570 within VDR gene, interaction between rs699947 and rs2228570, rs2228570 andsmoking were all associated with increased MM risk.

Protective effect of ginseng fruit anthocyanins against acetaminophen-induced liver damage in mice / 中草药

Objective: To investigate the protective effect of ginseng fruit anthocyanins (GFA) against acetaminophen (AP) induced liver damage in mice and its possible mechanism. Methods: The model of AP induced liver injury was established, and the GFA protection for liver damage was observed. Thirty-two male ICR mice were randomly divided into normal group, AP group, GFA with 200 mg/kg dose group, and GFA with 400 mg/kg group. Colorimetric method was used to assay the contents of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), activity of glutathione (GSH) and malondialdehyde (MDA) content of liver homogenate in mice, and observe liver tissue pathological section. Results: GFA obviously reduced the level of ALT in serum, inhibited the level of MDA, and enhanced activity of GSH in liver tissue. The H&E and Hoechst 33258 staining results indicated that GFA could obviously improve the degree of liver tissue necrosis and apoptosis, narrow the scope of necrosis, and relieve the inflammatory cell infiltration. By inflammatory factor of iNOS, COX-2 immunohistochemical staining and nitrification stress index of 3-NT immunofluorescence, GFA could inhibit nitration stress and the expression of inflammatory cytokines. Conclusion: GFA has certain protective effect on AP-induced acute liver injury and its mechanism may relate to antioxidant effect, inhibition of nitrification stress, alleviation inflammation reaction and inhibiting apoptosis.

The 100 most cited articles in ectopic pregnancy: a bibliometric analysis.

Ectopic pregnancy (EP) remains a major gynecological emergency and is a cause of morbidity or even mortality in women. As a consequence, top citation analysis of EP research in database of the Science Citation Index Expanded is needed to assess the publication trends of leading countries/territories and institutes as well as the research hotspots of EP. A total of 4881 articles relevant to EP were retrieved in the database of the Science Citation Index Expanded from 1965 to present, in which the 100 top-cited articles were selected for further analysis. The number of citations ranged from 81 to 482 (131.57 ± 69.76), with a time span of 40 years between 1969 and 2009. These citation classics came from 14 countries, and 65 of the articles came from the United States. Yale University in Connecticut led the list of classics with six papers. The 100 top-cited articles were published in 32 journals, in which the journal of Fertility and Sterility published the most (23 papers). Stovall TG and Ling FW published the highest number of studies (6 papers each). Articles that originated in the United States and that were published in high-impact journals were most likely to be cited in the field of EP research. Bibliometric analysis was used to provide a historical perspective on the progress in EP research over the past 50 years. Citation analysis is a feasible tool to comprehensively recognize the advances of EP research in the past and future research.