Study on the mechanism of warming yang and reducing turbidity decoction in the treatment of diabetic kidney disease based on network pharmacology.

This study aimed to investigate the mechanism of warming yang and reducing turbidity decoction in the treatment of diabetic kidney disease (DKD) by network pharmacology. The active components and corresponding targets of warming yang and reducing turbidity decoction were screened through the Traditional Chinese Medicine Systems Pharmacology database, DKD-related targets were obtained from Genecard and Online Mendelian Inheritance in Man databases, and drug-disease common targets were screened through Venny online website. Then we used STRING and Cytoscape software to analyze and perform protein-protein interaction network, and used CytoNCA plug-in to perform topological analysis to screen out the core target. We used RStudio to performed gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. One hundred one active components in warming yang and reducing turbidity decoction participated in the regulation of the body's response to foreign bodies, lipopolysaccharides, metal ions, ketone bodies, hypoxia and oxidative stress by regulating 186 targets related to DKD, and played a role in the treatment of DKD by interfering with pathways such as interfered with lipids and atherosclerosis, PI3K-Akt, fluid shear stress and atherosclerosis, AGE-RAGE and cell senescence. It was implied that warming yang and reducing turbidity decoction had the features of multi components, multi targets and multi pathways in the treatment of DKD, which might create methods and directions for further verification of the molecular mechanism of warming yang and reducing turbidity decoction.

Efficacy of relative dose intensity of nab-paclitaxel for the short-term outcomes, survival, and quality of life in patients with advanced pancreatic cancer: a retrospective study.

Background: To optimize treatment, choosing the appropriate relative dose intensity (RDI) of nab-paclitaxel is an important way to improve patient tolerance, therapeutic efficacy, and survival. However, few studies have focused on the efficacy of the RDI of nab-paclitaxel in patients with advanced pancreatic cancer, and whether the RDI of nab-paclitaxel could be employed as an index for treatment remains unknown. To explore the relationship between RDI of nab-paclitaxel and chemotherapy efficacy, survival, quality of life (QoL), and adverse effects in patients with advanced pancreatic cancer. Methods: In this retrospective study, a total of 32 patients with advanced pancreatic cancer, ECOG score of 0 to 2 were included from January 2017 to March 2020. The patients were treated with nab-paclitaxel combined with gemcitabine as a first-line treatment and divided into high and low RDI groups. Chemotherapy efficacy, survival, QoL, and adverse effects between two groups were compared. Results: The disease control rate (DCR) was 20.0% in the low RDI group, compared with 81.8% in the high RDI group (P=0.002). A good correlation between nab-paclitaxel RDI and short-term efficacy was observed in all 32 patients (r=0.728, P<0.01). Furthermore, the high RDI group had significantly better median overall survival (mOS: 12 vs. 8 months, P=0.034) and median progression-free survival (mPFS: 5.5 vs. 3 months, P=0.052) compared to that of low RDI patients. Univariate regression analysis showed that longer overall survival was associated with lower ECOG score [hazard ratio (HR): 10.88; 95% confidence interval (CI): 2.54-46.5, P=0.001], tumors located in the body or tail of pancreases (HR: 3.82; 95% CI: 1.4-10.3, P=0.0081), and higher RDI (HR: 0.21; 95% CI: 0.071-0.6, P=0.004). The high RDI group had a significantly better physical function and emotional function improvement compared to the low RDI group (P<0.05). Moreover, high RDI did not increasing the severity and frequency of the adverse events. Conclusions: It is recommended to maintain a sufficient RDI of nab-paclitaxel to ensure that the balance between lerability, therapeutic efficacy, and survival benefits is satisfied in patients with advanced pancreatic cancer.

Transcriptomic Insight into Viviparous Growth in Water Lily.

Water lily is an important ornamental flower plant which is capable of viviparous plantlet development. But no study has been reported on the molecular basis of viviparity in water lily. Hence, we performed a comparative transcriptome study between viviparous water lily Nymphaea micrantha and a nonviviparous species Nymphaea colorata at four developmental stages. The higher expression of highly conserved AUX/IAA, ARF, GH3, and SAUR gene families in N. micrantha compared to N. colorata is predicted to have a major impact on the development and evolution of viviparity in water lily. Likewise, differential regulation of hormone signaling, brassinosteroid, photosynthesis, and energy-related pathways in the two species provide clues of their involvement in viviparity phenomenon. This study revealed the complex mechanism of viviparity trait in water lily. The transcriptomic signatures identified are important basis for future breeding and research of viviparity in water lily and other plant species.

LncRNA TUG1 exhibits pro-fibrosis activity in hypertrophic scar through TAK1/YAP/TAZ pathway via miR-27b-3p.

Hypertrophic Scar (HS) is a complicated fibrotic disease. In addition, its pathogenesis is still to be further explored. Long non-coding RNAs (lncRNAs) have been proved to be participated in multiple diseases, including HS. However, the role of lncRNA TUG1 in HS remains unclear. The expression level of RNA and protein in cells were detected by q-PCR and western blot, respectively. MTT assay was performed to test the cell proliferation. Cell migration was detected by transwell assay. Cell apoptosis was measured by flow cytometry. Dual luciferase report assay and RNA pull down were used to verify the relationship between TUG1, miR-27b-3p and TAK1.TUG1 and TAK1 were upregulated in HS, while miR-27b-3p was downregulated. Knockdown of TUG1 significantly suppressed the proliferation and migration and induced the apoptosis of HS fibroblasts (HSF). In addition, silencing of TUG1 notably inhibited the extracellular matrix (ECM) biosynthesis in HSF. Overexpression of miR-27b-3p has the same effect on HS as that of TUG1 knockdown. Meanwhile, TUG1 could sponge miR-27b-3p, and TAK1 was the direct target of miR-27b-3p. Furthermore, knockdown of TUG1 significantly suppressed the fibrosis in HS via miR-27b-3p/TAK1/YAP/TAZ axis mediation. LncRNA TUG1 promotes the fibrosis in HS via sponging miR-27b-3p and then activates TAK1/YAP/TAZ pathway, which may serve as a potential target for treatment of HS.

Pattern of distant metastases and predictive nomograms in colorectal mucinous adenocarcinoma: a SEER analysis.

BACKGROUND: We evaluated the metastatic patterns and explored the prognostic value of distant metastasis pattern in patients with metastatic colorectal mucinous adenocarcinoma (MC) using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Between 2010 and 2015, newly diagnosed colorectal MC patients were selected using the SEER database. Patient prognosis was compared based on the clinicopathological parameters, treatment method, and the site and number of metastatic organs. Cox analyses were used to identify factors associated with overall survival (OS). A nomogram was built to predict the patient's survival. Harrell's concordance index (c-index) and calibration curves were used to analyze the discriminative ability of the prognostic factors. RESULTS: Of 3,088 patients diagnosed with colorectal MC, the liver was the only metastatic organ in 78.4% (997/1,271) of all liver metastasis cases, the lung was the only metastatic organ in 41.0% (164/400) of all lung metastasis cases, bone was the only metastatic organ in 26.6% (29/109) of all bone metastasis cases, and the brain was the only metastatic organ in 23.5% (4/17) of all brain metastasis cases. Compared with the untreated cases, those treated with chemotherapy, surgery, and radiotherapy had better OS (P<0.001). There were marked OS differences (P<0.001) between patients with and without liver and bone metastases. Patients with bone metastasis had the best survival, while those with brain metastasis had the worst survival (P<0.001). Patients with one metastatic site had better prognosis compared to those with two or three (P<0.001). Patients with liver metastasis had the best survival, while those with bone and brain metastasis had the worst survival (P<0.001). Multivariate analysis showed that age <65 years, non-black race, grade I, N0 stage, chemotherapy, radiation, surgery, liver metastasis, and bone metastasis were independent prognostic factors. A nomogram was constructed to predict survival probability. The c-index value was up to 0.745. The calibration plot showed that the nomogram was clinically useful. CONCLUSIONS: Metastatic MC (mMC) patients had a characteristic distant metastasis pattern. This study constructed a new and sufficiently accurate prognostic model of mMC based on population-based data. These findings can be utilized to predict prognosis and guide mMC patient management.

Identification of GOLM1 as a positively regulator of tumor metastasis by regulating MMP13 in gastric carcinoma.

BACKGROUND: Metastatic gastric carcinoma (GC) is a typically incurable disease. The progression of anti-metastatic treatment is hampered because the underlying mechanisms regulating the metastasis of GC cell are not well illuminated. OBJECTIVE: Therefore, further elucidation of the molecular mechanism behind the metastatic traits of GC cells is needed for optimizing GC treatment. METHODS: The levels of GOLM1 and MMP13 in GC cells and tissues were measured by using qPCR assay. The growth of GC cells in vitro was detected using MTS and colony formation assays. The migration and invasion of GC cells was analyzed using wound healing test and Transwell invasion assay. The level of MMP13 in GC cell was measured using immunoblotting and the level of GOLM1 was measured using immunofluorescence staining. The role of GOLM1 on the distant metastasis of GC SGC7910 cell was analyzed using experimental metastasis assay. Transplanted tumor model was constructed to analyze the influence of GOLM1 on GC cell growth in vivo. RESULTS: Here, we report that GOLM1 is over-expressed in GC and knockdown GOLM1 impairs the aggressive phenotypes of GC cell in vitro. Furthermore, downregulation of GOLM1 restrains the tumor growth of GC cell in nude mice. Nevertheless, upregulation of GOLM1 distinctly elevated the growth, migration ability and invasiveness of GC SGC7910 cell. Finally, GOLM1 increases the metastatic phenotypes of GC cell in a MMP13-dependent manner. CONCLUSIONS: Altogether, this investigation demonstrates the crucial function of GOLM1 in the progression of GC, which indicating GOLM1 as a potential target for GC treatment.

VEGFR2 promotes tumorigenesis and metastasis in a pro-angiogenic-independent way in gastric cancer.

BACKGROUND: VEGF/VEGFR2 pathway is the central therapeutic target in anti-angiogenic treatment in multiple cancers. However, little work has been carried out concerning the pro-malignancy functions of VEGFR2 that are independent of its pro-angiogenesis effects in gastric cancer. Here, we demonstrated that VEGFR2 up-regulation in gastric cancer tissues was a prognostic marker for poor disease-free survival and overall survival of gastric cancer patients. METHODS: Immunohistochemistry was used to detect VEGFR2 and VTN expressions in specimens. Kaplan-Meier curves were constructed for survival analysis. Stably knockdown cell lines and overexpression cell lines were constructed by small interfering RNA and plasmids transfection. Real-time PCR and Western blot were used to confirm the expressions of target genes at both RNA and protein levels. Cell proliferation was measured by using Cell Counting Kit-8 and xenograft models. Microarray and bioinformatic analysis were also performed to identify the relationship between Vitronectin (VTN) and VEGFR2. RESULTS: When overexpressed in gastric cancer cells, VEGFR2 increased cellular proliferation and invasion in vitro and tumor formation in xenograft models. By using integrating microarray and bioinformatic analysis, we identifiedVTN as a downstream of VEGFR2 pathway. In gain- and loss-of function analysis in gastric cancer cells, VTN was further verified in consistent with VEGFR2 in expression levels and in regulating cell growth and motility in vitro and in vivo. Moreover, in gastric cancer samples, VTN was as also revealed as a poor prognostic factor. CONCLUSIONS: Our present findings defined a novel activity for VEGFR2 in promoting tumorogenicity, motility and indicating a poor survival in gastric cancer beyond its known pro-angiogenic effects. IMPLICATIONS: Our present findings defined a novel activity for VEGFR2 in promoting tumorogenicity, motility and indicating a poor survival in gastric cancer beyond its known pro-angiogenic effects, which may provide a new and valuable target for design of therapies for intervention and a new cognitive perspective for the anti-angiogenesis therapies.

Intrathecal morphine verse femoral nerve block for pain control in total knee arthroplasty: A meta-analysis from randomized control trials.

OBJECTIVE: Total knee arthroplasty (TKA) is usually associated with postoperative pain. The objective of this systematic review and meta-analysis was to evaluate the effectiveness and safety of femoral nerve block compared with intrathecal morphine for pain management after TKA. METHODS: Potentially relevant literature was identified from electronic databases including Medline, PubMed, Embase, ScienceDirect and the Cochrane Library. Gray academic studies were also identified from the reference of included literature. There was no language restriction. Pooling of data was carried out using Stata 11.0. RESULTS: Four randomized controlled trials (RCTs) involving 185 patients met the inclusion criteria. The meta-analysis indicated that there were no significant differences in terms of Visual Analog Scale (VAS) score at 6 h (standard mean difference (SMD) = -0.09, 95% CI: -1.62 to 1.43, P = 0.903), 12 h (weighted mean difference (WMD) = 1.84, 95% CI: -8.01 to 11.69, P = 0.714) or 24 h (WMD = 1.56, 95% CI: -14.31 to 17.42, P = 0.8474). No significant difference were found regarding morphine consumption at 6 h (WMD = -0.84, 95% CI: -2.52 to 0.85, P = 0.332), 12 h (WMD = 0.031, 95% CI: -3.304 to 0.3366, P = 0.985), 24 h (WMD = 0.21, 95% CI: -7.32 to 7.75, P = 0.956) or incidence of postoperative vomit and nausea (risk difference (RD) = -0.01, 95% CI: -0.15 to 0.12, P = 0.847). There was a significant difference between the groups in terms of the risk of itching postoperatively (RD = 0.41, 95% CI: 0.29 to 0.54, P < 0.001). CONCLUSIONS: Femoral nerve block provides equal postoperative pain control compared with intrathecal morphine following total knee arthroplasty, although there were fewer side effects in the FNB groups. In contrast, FNB was performed with an additional procedure and required a special apparatus. Both methods are effective at pain control following TKA.

[Prevalence of thyroid nodules and influencing factors among employees of a company in Qingdao].

OBJECTIVE: To investigate the prevalence of thyroid nodules and influencing factors among employees of a company in Qingdao. METHODS: Through questionnaires, physical examination, thyroid ultrasonography and urinary iodine test, personal health information and examinations of thyroid nodules of 9612 serving and retired employees in a company in 2010 who had lived in Qingdao for more than 5 years were collected to investigate the prevalence of thyroid nodules and its influencing factors. RESULTS: The prevalence of thyroid nodules was 36.56% (3514/9612). The prevalence rates of single nodules and multiple nodules were 18.39% (1768/9612) and 18.16% (1746/9612) respectively. With increasing urinary iodine level, the prevalence of multiple thyroid nodules decreased from 25.51% (366/14350)(urinary iodine < or = 100 microg/L) to 12.99% (214/1648) (urinary iodine > 300 microg/L) showing a clear downward trend (chi2 = 67.11, P < 0.01). The prevalence rates of thyroid nodules among males and females were 31.28% (2283/7299) and 53.22% (1231/2313) (P < 0.01) respectively. With increasing age, the prevalence of thyroid nodules gradually increased from 7.95% (67/843) (19 - 29 years old) to 58.81% (267/454) ( >70 years old) among males and increased from 23.74% (33/139) (19 - 29 years old) to 80.38% (127/158) ( >70 years old) among females. The prevalence of thyroid nodules among males and females showed an increasing trend with age (male: chi2 = 434.12, P < 0.01; female: chi2 = 40.74, P < 0.01). The results of logistic regression showed that compared with males, females were more susceptible to thyroid nodules (OR = 2.809, 95% CI: 2.444 - 3.228). Smoking (OR = 1.394, 95% CI: 1.249 - 1.556), hypertension (OR = 1.155, 95% CI: 1.040 - 1.282), diabetes ( OR = 1.228, 95% CI: 1.039 - 1.452) and overweight (OR = 1.199, 95% CI: 1.078 - 1.333) might be risk factors for thyroid nodules after adjusting for age and gender. CONCLUSION: The prevalence of thyroid nodules was high among the employees. In order to reduce the thyroid nodules, smoking cessation and weight control should be promoted. Blood pressure and glucose level should be actively controlled for patients with hypertension and (or) diabetes.

[Preliminary establishment of transplanted human chronic myeloid leukemia model in nude mice].

Chronic myeloid leukemia (CML) is a malignant clonal disease derived from hematopoietic stem cells. CML stem cells were thought to be the root which could lead disease development and ultimately rapid change. However, a stable animal model for studying the characteristics of CML stem cells is currently lacking. This study was aimed to establish a transplanted human CML nude-mice model to further explore the biological behavior of CML stem cells in vivo, and to enrich CML stem cells in nude mice by series transplantation. The 4 - 6 weeks old BALB/c nude mice pretreated by splenectomy (S), cytoxan intraperitoneal injection (C) and sublethal irradiation (I) were transplanted intravenously with (5 - 7) × 10(7) of bone marrow mononuclear cells from CML patients in chronic phase. Alternatively, 4 - 6 weeks old BALB/c nude mice pretreated by lethal irradiation were transplanted intravenously with 5 × 10(6) homologous bone marrow cells of BALB/c nude mice together with (5 - 7) × 10(7) of bone marrow mononuclear cells from CML patients in chronic phase simultaneously. The leukemic cells engrafted and infiltrated in organs and bone marrow of the mice were tracked by reverse transcription-polymerase chain reaction (RT-PCR), plastic-embedded biopsy and flow cytometry. The results of these two methods were compared. The results showed that human CML cells engrafted and infiltrating into the bone marrow of two nude mice pretreated with SCI could be detected. In spite of the low successful rate, results suggested the feasibility of this method by using BALB/c nude mice as a human CML animal model. In contrast, in nude mice pretreated by the lethal dose irradiation, CML cells in the bone marrow could not be found. It is concluded that human bone marrow CML cells can results in leukemia in nude mice pretreated by SCI. Thus this study provides a new strategy for establishment of CML animal models which deserves further elaboration.