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1.
Chin J Nat Med ; 19(11): 801-814, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34844719

RESUMO

Pulmonary hypertension (PH) is a severe pathophysiological condition characterized by pulmonary artery remodeling and continuous increases in pulmonary artery pressure, which may eventually develop to right heart failure and death. Although newly discovered and incredible treatment strategies in recent years have improved the prognosis of PH, limited types of effective and economical drugs for PH still makes it as a life-threatening disease. Some drugs from Chinese materia medica (CMM) have been traditionally applied in the treatment of lung diseases. Accumulating evidence suggests active pharmaceutical ingredients (APIs) derived from those medicines brings promising future for the prevention and treatment of PH. In this review, we summarized the pharmacological effects of APIs derived from CMM which are potent in treating PH, so as to provide new thoughts for initial drug discovery and identification of potential therapeutic strategies in alternative medicine for PH.

2.
Cell Death Dis ; 12(11): 1051, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34741014

RESUMO

PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy.

3.
Bioengineered ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34753396

RESUMO

Colorectal cancer (CRC) is the third most commonly diagnosed malignant tumor worldwide. LINC00857 has been reported as a dysregulated long non-coding RNAs (lncRNAs) involved in the genesis and development of different cancers. In CRC, accumulating evidence indicates that high mobility group box 3 (HMGB3) is over-expressed and contributes to CRC development. However, the mechanism underlying HMGB3 upregulation in CRC remains unclear. The present work aims to investigate the role of LINC00857 and its functional interaction with HMGB3 in regulating CRC progression. Differential expression of LINC00857 between CRC tissues and normal tissues was identified in TCGA (The Cancer Genome Atlas) database. In vitro functional assays were performed to explore the biological functions of LINC00857 in CRC cells. In vivo xenograft model was employed to investigate the role of LINC00857 in CRC tumorigenesis. We found that LINC00857 was significant upregulated in CRC tissues and cell lines. LINC01207 knockdown significantly inhibited the proliferation, migration and invasion of CRC cells, and also induced apoptosis. Moreover, LINC00857 knockdown suppressed CRC tumorigenesis in vivo. We further demonstrated that the effects of LINC00857 in CRC cells were mediated through miR-150-5p/HMGB3 axis. LINC00857 negatively regulates the activity of miR-150-5p, which releases its inhibition on HMGB3 expression. Our data indicate that LINC00857/miR-150-5p/HMGB3 axis plays a fundamental role in regulating the malignant phenotype and tumorigenesis of CRC. Targeting this axis may serve as novel therapeutic strategies for CRC treatment.

4.
Asian J Androl ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34755700

RESUMO

Individualized treatment of prostate cancer depends on an accurate stratification of patients who are sensitive to various treatments. Interleukin-23 (IL-23) was reported to play a significant role in prostate cancer. Here, we aimed to explore the clinical value of IL-23-secreting (IL-23+) cells in prostate cancer patients. We evaluated interleukin-23A (IL-23A) expression in The Cancer Genome Atlas database and retrospectively enrolled 179 treatment-naïve metastatic prostate cancer patients diagnosed in our institute between June 2012 and December 2014. IL-23+ cells were stained and evaluated via immunohistochemistry. Further, survival and multivariate Cox regression analyses were conducted to explore the prognostic value of IL-23+ cells. We found that IL-23A expression correlated with disease progression, while IL-23+ cells were clearly stained within prostate cancer tissue. Patients with higher Gleason scores and multiple metastatic lesions tended to have more IL-23+ cell infiltration. Further analyses showed that patients with higher levels of IL-23+ cells had significantly worse overall survival (hazard ratio [HR] = 2.996, 95% confidence interval [95% CI]: 1.812-4.955; P = 0.001) and a higher risk of developing castration resistance (HR = 2.725, 95% CI: 1.865-3.981; P = 0.001). Moreover, subgroup analyses showed that when patients progressed to a castration-resistant status, the prognostic value of IL-23+ cells was observed only in patients treated with abiraterone instead of docetaxel. Therefore, we showed that high IL-23+ cell infiltration is an independent prognosticator in patients with metastatic prostate cancer. IL-23+ cell infiltration may correlate with abiraterone effectiveness in castration-resistant prostate cancer patients.

5.
Int J Gen Med ; 14: 7869-7883, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795508

RESUMO

Background: To explore the baseline characteristics, pathological and survival outcomes of Asian-American patients with clear cell renal cell carcinoma (ccRCC), and make comparisons with White patients. Materials and Methods: In this study, patients diagnosed with ccRCC between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Basic characteristics of Asian-American patients were analysed and compared with White patients. Then, proportional mortality ratio (PMR) analyses were performed in Asian population to investigate the proportions of different cause of deaths (CODs), and make comparisons with White patients. Moreover, Kaplan-Meier (KM) analyses were developed to investigate the survival disparities of ccRCC patients between Asian-Americans and White patients. Finally, a competing risk regression model was constructed to identify potential prognostic factors for ccRCC patients in the whole population. Results: A total of 1586 Asian-American patients were eventually identified, and the median age at diagnosis was 61 years old. In Asian patients, those from South Asian had the youngest age at diagnosis (P<0.001) and the earliest stage of diseases (localized: 76.83%, T1: 70.73%, all P<0.05) when compared with other ethnicities. No significant differences were detected in tumor characteristics between Asian-Americans and White patients. Older age (P<0.001), earlier stage (P<0.001) and the administration of surgery (P=0.050) were tightly associated with a lower risk of dying of RCC in Asian-American patients. Additionally, Asian-American patients had comparable survival outcomes when compared with White patients. Lastly, competing risk regression model revealed that age at diagnosis (P<0.001), tumor grade (P<0.001), histological stage (P<0.001), median household income (P<0.001) and the administration of surgery (P<0.001) were prognostic factors for cancer-specific survival (CSS) in ccRCC patients, while died of other causes was regarded as a competing event. Conclusion: Asian-American patients had similar tumor characteristics and survival outcomes with White patients. In Asian patients, those from South Asian had the youngest age at diagnosis and the earliest stage of diseases. Age, grade, histological stage, household income and surgery were identified to be closely related to CSS in ccRCC patients. In the future, prospective and well-designed studies are needed to verify our findings.

6.
Langmuir ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793174

RESUMO

The opal-like SiO2 microcarriers with different pore diameters named opal-SiO2I and opal-SiO2II were synthesized and utilized as microcarriers to immobilize Rhizopus oryzae lipase (ROL) and Aspergillus oryzae α-amylases (AOA). ROL and AOA can be more stably immobilized on the cross-linked SiO2 opals by neopentyl glycol diglycidyl ether (NGDE), which is the first attempt to use it as a cross-linking agent compared with glutaraldehyde. According to the morphology analysis, multiple layers of SiO2 monodisperse microspheres were regularly packed and formed an opal-like structure, and enzymes were well scattered and immobilized throughout the SiO2 opals. The results showed that the performance of enzymes immobilized on opal-SiO2II with a larger specific surface area was much better than that of opal-SiO2I. The enzyme activity of ROL@opal-SiO2II and AOA@opal-SiO2II cross-linked with 1% NGDE increased 5.32 and 9.32 times compared with their free counterpart, respectively. Furthermore, pH and thermal stability and reusability of ROL/AOA@opal-SiO2II were significantly improved and higher than those of ROL/AOA@opal-SiO2I and free enzymes. This study provides an easily obtained microcarrier opal-SiO2II, which shows potential for efficient different enzyme immobilizations and further industrial applications.

7.
Mater Horiz ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34666341

RESUMO

The rapid development of non-fullerene acceptors (NFAs) with strong near-infrared absorption has led to remarkably enhanced short-circuit current density (Jsc) values in organic solar cells (OSCs). NFAs based on the benzotriazole (Bz) fused-ring π-core have great potential in delivering both high Jsc and decent open-circuit voltage values due to their strong intramolecular charge transfer with reasonably low energy loss. In this work, we have designed and synthesized a series of Bz-based NFAs, PN6SBO-4F, AN6SBO-4F and EHN6SEH-4F, via regiospecific N-alkyl engineering based on the high-performance NFA mBzS-4F that was reported previously. The molecular packing of mBzS-4F, AN6SBO-4F, and EHN6SEH-4F single crystals was analyzed using X-ray crystallography in order to provide a comprehensive understanding of the correlation between the molecular structure, the charge-transporting properties, and the solar cell performance. Compared with the typical honeycomb single-crystal structure of Y6 derivatives, these NFAs exhibit distinctly different molecular packing patterns. The strong interactions of terminal indanone groups in mBzS-4F and the J-aggregate-like packing in EHN6SEH-4F lead to the formation of ordered 3D networks in single-crystals with channels for efficient charge transport. Consequently, OSCs based on mBzS-4F and EHN6SEH-4F show efficient photon-to-current conversions, achieving the highest power conversion efficiency of 17.48% with a Jsc of 28.83 mA cm-2.

8.
World J Clin Cases ; 9(26): 7762-7771, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34621826

RESUMO

BACKGROUND: Postoperative ileus is a frequent postoperative complication, especially after abdominal surgery. Sympathetic excitation is the primary factor for postoperative ileus. Sympathetic activation becomes increased by surgical stress, postoperative pain, and inflammation. Dexmedetomidine (DEX) can inhibit sympathetic nerve activity, inflammation, and pain. AIM: To observe whether DEX promotes bowel movements in patients after laparoscopic nephrectomy. METHODS: One hundred and twenty patients undergoing laparoscopic nephrectomy were assigned to three groups: C (normal saline infusion), D1 (DEX 0.02 µg/kg/h), and D2 (DEX 0.04 µg/kg/h). The primary outcomes were the recorded times to first flatus, defecation, and eating after surgery. The secondary outcomes were postoperative pain, assessed using the numerical rating scale (NRS), adverse effects, and the duration of the postoperative hospital stay. RESULTS: The times to first flatus, defecation, and eating in groups D1 and D2 were significantly shorter than those in group C (P < 0.01). The NRS scores at 8 h and 24 h after surgery were significantly lower in groups D1 and D2 than in group C (P < 0.05). No adverse effects were observed (P > 0.05). CONCLUSION: Postoperative infusion of DEX at 0.04 µg/kg/h facilitates bowel movements in patients undergoing laparoscopic nephrectomy.

9.
Biotechnol Prog ; : e3218, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34601810

RESUMO

The Candida antarctica lipase B (CALB) was embedded in the metal-organic framework, zeolitic imidazolate framework-8 (ZIF-8), and applied in the enzymatic synthesis of L-ascorbic acid palmitate (ASP) for the first time. The obtained CALB@ZIF-8 achieved the enzyme loading of 80 mg g-1 with 11.3 U g-1 (dry weight) unit activity, 59.8% activity recovery, and 92.7% immobilization yield. Under the optimal condition, ASP was synthesized with over 75.9% conversion of L-ascorbic acid in a 10-batch reaction. Continuous synthesis of ASP was subsequently performed in a packed bed bioreactor with an outstanding average space-time yield of 58.1 g L-1  h-1 , which was higher than ever reported continuous ASP biosynthesis reactions.

10.
Materials (Basel) ; 14(20)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34683787

RESUMO

Polyurethane elastomer (PUE) has attracted much attention in impact energy absorption due to its impressive toughness and easy processability. However, the lack of continuous impact resistance limits its wider application. Here, an amino-siloxane (APTES) grafted WS2-coated MWCNTs (A-WS2@MWCNTs) filler was synthesized, and A-WS2@MWCNTs/PUE was prepared by using the filler. Mechanical tests and impact damage characterization of pure PUE and composite PUE were carried out systematically. Compared with pure PUE, the static compressive strength and dynamic yield stress of A-WS2@MWCNTs/PUE are increased by 144.2% and 331.7%, respectively. A-WS2@MWCNTs/PUE remains intact after 10 consecutive impacts, while the pure PUE appears serious damage after only a one-time impact. The improvement of mechanical properties of A-WS2@MWCNTs/PUE lies in the interfacial interaction and synergy of composite fillers. Microscopic morphology observation and damage analysis show that the composite nanofiller has suitable interfacial compatibility with the PUE matrix and can inhibit crack growth and expansion. Therefore, this experiment provides an experimental and theoretical basis for the preparation of PUE with excellent impact resistance, which will help PUE to be more widely used in the protection field.

11.
Pharmaceutics ; 13(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34683879

RESUMO

Antibiotic resistance has become a worldwide public health threat due to the rapid evolution and spread of antibiotic-resistant bacteria. CCG-211790 is a novel anti-virulence compound that does not kill bacteria but could ameliorate human diseases by inhibiting expression of virulence factors, thereby applying less selection pressure for antibiotic resistance. However, its potential clinical use is restricted because of its poor aqueous solubility, resulting in formulation challenges. Nanosuspension technology is an effective way to circumvent this problem. Nanosuspensions of CCG-211790 with two different particle sizes, NanoA (315 ± 6 nm) and NanoB (915 ± 24 nm), were prepared using an antisolvent precipitation-ultrasonication method with Tween 80 as the stabilizer. Particle and pharmacokinetics (PK) of CCG-211790 nanosuspensions were characterized. Both NanoA and NanoB demonstrated remarkable increases in dissolution rate compared with the bulk compound. The PK parameters of NanoA were comparable to those of CCG-211790 solution formulation in intravenous or oral administration, suggesting that CCG-211790 nanosuspensions with smaller particle size improved oral bioavailability and drug exposure compared to traditional formulations of drug candidates.

12.
Front Immunol ; 12: 754961, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691076

RESUMO

Background: Transarterial chemoembolization (TACE) stands for the most commonly utilized therapy for hepatocellular carcinoma (HCC) worldwide. This study was to explore the potential predictive and prognostic roles of LAG-3 and PD-L1 as serum biomarkers in HCC patients underwent TACE treatment. Methods: A total of 100 HCC patients receiving TACE as well as 30 healthy controls were enrolled in the study. Serum LAG-3 and PD-L1 levels were determined at baseline and 3 day after TACE using enzyme-linked immunosorbent assay (ELISA). Results: We found serum levels of LAG-3 and PD-L1 were significantly elevated in HCC patients compared with healthy controls. Interestingly, patients with low pre-TACE and post-TACE levels of LAG-3 but not PD-L1 had a high probability of achieving an objective response (OR) after TACE treatment. Additionally, high pre-TACE LAG-3 level was correlated with poor disease outcome, and the patients with both high serum LAG-3 and PD-L1 level had the shorter overall survival (OS) than patients who are either PD-L1 or LAG-3 high or both PD-L1 and LAG-3 low. High pre-TACE serum LAG-3 level was positively associated with more cirrhosis pattern, advanced BCLC stage, pre-TACE alanine aminotransferase (ALT) level, and pre-TACE aspartate aminotransferase (AST) level. Furthermore, in 50 patients who underwent TACE, the serum LAG-3 level was significantly decreased at 3 day after TACE. Conclusion: Both pre-TACE and post-TACE serum LAG-3 levels could serve as powerful predictors for tumor response of TACE, and high pre-TACE serum LAG-3 level was an indicator for poor prognosis in HCC.

13.
Front Med (Lausanne) ; 8: 731254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660639

RESUMO

Background: Myofascial trigger points (MTrPs) injection has been effectively used for the management of chronic painful diseases. Latent MTrPs can induce autonomic nerve phenomena. In our clinic, we observed that allergic rhinitis (AR) symptoms significantly improved when latent MTrPs injection was performed for migraine. Objective: To compare the efficacy and safety between latent MTrPs injection and sublingual immunotherapy (SLIT) in patients with persistent, moderate to severe AR. Methods: This randomized controlled trial was conducted with 112 patients with AR. Patients were randomized to receive SLIT (n = 56) or latent MTrPs injection. Total nasal symptom score (TNSS, n = 56), nasal symptoms, medication days, and adverse events were evaluated during the 9 months follow-up period after treatment in both groups. Results: Latent MTrPs injection significantly reduced TNSS to a greater level from baseline (from 8.36 ± 1.96 to 4.43 ± 2.18) than SLIT (from 8.66 ± 2.31 to 7.80 ± 2.47) at week 1 (P < 0.001), and sustained the improvement in symptoms throughout to month 9. Latent MTrPs showed statistically significant differences vs. SLIT for the TNSS reduction both at month 2 (6.59 ± 2.37 vs. 2.64 ± 2.38; p < 0.001) and month 3 (4.59 ± 2.77 vs. 2.62 ± 2.43; p <0.001). Latent MTrPs also showed a better improvement in the onset time of efficacy compared with SLIT. Adverse reactions were few and non-serious in both treatment groups. Conclusions: Latent MTrPs injection significantly improved symptoms and decreased symptom-relieving medication use in patients with AR and was well tolerated. Clinical Trials Registration: Chinese Clinical Trial Registry, ChiCTR1900020590. Registered 9 January 2019, http://www.chictr.org.cn/index.aspx.

14.
Sci Rep ; 11(1): 21118, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702904

RESUMO

Microalgal-bacterial consortium is an effective way to meet increasingly stringent standards in wastewater treatment. However, the mechanism of wastewater removal effect has not been properly explained in community structure by phycosphere. And little is known about that the concept of macroecology was introduced into phycosphere to explain the phenomenon. In the study, the algal-bacterial consortia with different ratios of algae and sludge were cultured in same aerobic wastewater within 48 h in photobioreactors (PSBRs). Community structure at start and end was texted by metagenomic analysis. Bray-Curtis similarities analysis based on microbial community showed that there was obvious convergent succession in all consortia, which is well known as "convergence" in macroecology. The result showed that Bray-Curtis similarities at End (overall above 0.88) were higher than these at Start (almost less than 0.66). In terms of community structure, the consortium with 5:1 ratio at Start are the more similar with the consortia at End by which the maximum removal of total dissolved nitrogen (TDN, 73.69%), total dissolved phosphorus (TDP, 94.40%) and NH3-N (93.26%) in wastewater treatment process and biomass production (98.2%) higher than other consortia, according with climax community in macroecology with the highest resource utilization than other communities. Therefore, the macroecology can be introduced into phycosphere to explain the consortium for advanced wastewater treatment and optimization community structure. And the study revealed a novel insight into treatment effect and community structure of algal-bacterial consortia for advanced wastewater treatment, a new idea for to shortening the culture time of consortium and optimize predicting their ecological community structure and predicting ecological community.

15.
Sci Rep ; 11(1): 20159, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635711

RESUMO

Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2's expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.

16.
J Inorg Biochem ; 225: 111603, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34564032

RESUMO

Two iridium (III) polypyridine complexes [Ir(ppy)2(BIP)]PF6 (ppy = 2-phenylpyridine, BIP = 2-biphenyl-1H-imidazo[4,5-f][1,10]phenanthroline, Ir1), [Ir(piq)2(BIP)]PF6 (piq = 1-phenylisoquinoline, Ir2) and their liposomes Ir1lipo and Ir2lipo were synthesized and characterized. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cytotoxic activity against several cancer cells (A549, HepG2, SGC-7901, Bel-7402, HeLa) and non-cancer cell (mouse embryonic fibroblast, NIH3T3). The results showed that Ir1lipo displays the high cytotoxicity toward SGC-7901 with IC50 value of 5.8 ± 0.2 µM, while the complexes have no cytotoxicity toward A549, HepG2, Bel-7402 and HeLa cells. The cell colony demonstrated that the iridium (III) complexes-loaded liposomes can inhibit cell proliferation, induce cell cycle arrest at G0/G1 phase. Moreover, they also cause autophagy, induce a decrease of mitochondrial membrane potential and increase intracellular reactive oxygen species (ROS) content. These results suggest that the complexes encapsulated liposomes Ir1lipo and Ir2lipo inhibit the growth of SGC-7901 cells through a ROS-mediated mitochondrial dysfunction and activating the PI3K (phosphoinositide-3 kinase)/ AKT (protein kinase B) signaling pathways.

17.
Hum Brain Mapp ; 42(18): 5956-5972, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34541735

RESUMO

Formalin fixation has been shown to substantially reduce T2 estimates, primarily driven by the presence of fixative in tissue. Prior to scanning, post-mortem samples are often placed into a fluid that has more favourable imaging properties. This study investigates whether there is evidence for a change in T2 in regions close to the tissue surface due to fixative outflux into this surrounding fluid. Furthermore, we investigate whether a simulated spatial map of fixative concentration can be used as a confound regressor to reduce T2 inhomogeneity. To achieve this, T2 maps and diffusion tensor estimates were obtained in 14 whole, formalin-fixed post-mortem brains placed in Fluorinert approximately 48 hr prior to scanning. Seven brains were fixed with 10% formalin and seven brains were fixed with 10% neutral buffered formalin (NBF). Fixative outflux was modelled using a proposed kinetic tensor (KT) model, which incorporates voxelwise diffusion tensor estimates to account for diffusion anisotropy and tissue-specific diffusion coefficients. Brains fixed with 10% NBF revealed a spatial T2 pattern consistent with modelled fixative outflux. Confound regression of fixative concentration reduced T2 inhomogeneity across both white and grey matter, with the greatest reduction attributed to the KT model versus simpler models of fixative outflux. No such effect was observed in brains fixed with 10% formalin. Correlations between the transverse relaxation rate R2 and ferritin/myelin proteolipid protein (PLP) histology lead to an increased similarity for the relationship between R2 and PLP for the two fixative types after KT correction.

18.
Cancers (Basel) ; 13(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34572753

RESUMO

BACKGROUND: The laparoscopic approach in gastric cancer surgery is being increasingly adopted worldwide. However, studies focusing specifically on laparoscopic gastrectomy with D2 lymphadenectomy are still lacking in the literature. This retrospective study aimed to compare the short-term and long-term outcomes of laparoscopic versus open gastrectomy with D2 lymphadenectomy for gastric cancer. METHODS: The protocol-based, international IMIGASTRIC (International study group on Minimally Invasive surgery for Gastric Cancer) registry was queried to retrieve data on patients undergoing laparoscopic or open gastrectomy with D2 lymphadenectomy for gastric cancer with curative intent from January 2000 to December 2014. Eleven predefined, demographical, clinical, and pathological variables were used to conduct a 1:1 propensity score matching (PSM) analysis to investigate intraoperative and recovery outcomes, complications, pathological findings, and survival data between the two groups. Predictive factors of long-term survival were also assessed. RESULTS: A total of 3033 patients from 14 participating institutions were selected from the IMIGASTRIC database. After 1:1 PSM, a total of 1248 patients, 624 in the laparoscopic group and 624 in the open group, were matched and included in the final analysis. The total operative time (median 180 versus 240 min, p < 0.0001) and the length of the postoperative hospital stay (median 10 versus 14.8 days, p < 0.0001) were longer in the open group than in the laparoscopic group. The conversion to open rate was 1.9%. The proportion of patients with in-hospital complications was higher in the open group (21.3% versus 15.1%, p = 0.004). The median number of harvested lymph nodes was higher in the laparoscopic approach (median 32 versus 28, p < 0.0001), and the proportion of positive resection margins was higher (p = 0.021) in the open group (5.9%) than in the laparoscopic group (3.2%). There was no significant difference between the groups in five-year overall survival rates (77.4% laparoscopic versus 75.2% open, p = 0.229). CONCLUSION: The adoption of the laparoscopic approach for gastric resection with D2 lymphadenectomy shortened the length of hospital stay and reduced postoperative complications with respect to the open approach. The five-year overall survival rate after laparoscopy was comparable to that for patients who underwent open D2 resection. The types of surgical approaches are not independent predictive factors for five-year overall survival.

19.
Dis Markers ; 2021: 2863856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484467

RESUMO

Angiopoietin-like 3 (ANGPTL3), which is involved in new blood vessel growth, has been reported to exhibit an abnroaml expression in many different cancers. However, the expressing pattern and functions of ANGPTL3 renal cell carcinoma (RCC) were rarely reported. In this study, we observed that ANGPTL3 expression was distinctly downregulated in both RCC specimens from TCGA datasets and cell lines. Survival assays also revealed that patients with low ANGPTL3 expression exhibited a shorter overall survival and disease-free survival than those with high ANGPTL3 expression. Cell counting kit-8 (CCK-8) assay, Colony formation assay, and flow cytometry showed that overexpression of ANGPTL3 distinctly suppressed the proliferation of RCC cells, and promoted apoptosis. Transwell assays and Wound healing assays revealed that ANGPTL3 upregulation suppressed the migration and invasion of RCC cells. Then, we explored whether ANGPTL3 dysregulation influenced the alteration of Wnt/ß-catenin signaling using TOP/FOP flash reporter assays and western blot. The results showed that overexpression of ANGPTL3 distinctly suppressed the activity of Wnt/ß-catenin signaling. Overall, our results confirmed that overexpression of ANGPTL3 was related to the malignancy and good prognosis of RCC patients, and ANGPTL3 upregulation inhibited the tumor proliferation and metastasis via the Wnt/ß-catenin pathway. ANGPTL3 may be a novel therapeutic target and a prognostic biomarker for RCC patients.

20.
Ther Adv Chronic Dis ; 12: 2040622320967148, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471512

RESUMO

Background: Studies regarding the relationship of sclerostin (Scl) with clinical outcomes in patients undergoing maintenance haemodialysis have yielded controversial findings. This meta-analysis was performed to investigate the predictive role of Scl in this patient population. Methods: Several electronic medical databases (e.g. PubMed, Embase, Web of Science and Cochrane Library) were searched for eligible studies through December 20, 2019. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated based on Scr level (high or low) using a random or fixed effects model. Results: From among 641 initially screened publications, 16 eligible studies were included in this meta-analysis. A high Scl level was not associated with cardiovascular events [HR = 0.8 (95% CI, 0.42-1.35)] or all-cause mortality [HR = 0.93 (95% CI, 0.56-1.54)]. There was high heterogeneity, but no evidence of publication bias. Interestingly, a high Scl level was associated with reduced cardiovascular events [HR = 0.44 (95% CI, 0.29-0.69)] in the subgroup by shorter follow-up period or all-cause mortality [pooled HR = 0.58 (95% CI, 0.36-0.91)] by shorter dialysis vintage. Conclusion: This meta-analysis indicated that a high Scl level did not predict total clinical outcomes in patients undergoing maintenance haemodialysis despite survival benefits in the subgroups. The predictive role of Scl in these patients should be further evaluated in large prospective studies.

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