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The farnesoid X receptor (FXR) is a ligand-activated nuclear receptor. Activation of FXR significantly impacts the expressions of the pivotal genes involved in bile acid metabolism, inflammation, fibrosis, and homeostasis of lipid and glucose, leading to considerable interests in developing FXR agonists for the treatment of nonalcoholic steatohepatitis (NASH) or other FXR-relevant diseases. Herein, we describe the design, optimization, and characterization of a series of N-methylene-piperazinyl derivatives as the nonbile acid FXR agonists. Particularly, compound 23 (HPG1860), a potent full FXR agonist, shows high selectivity, favorable ADME and pharmacokinetics profile, along with favorable in vivo activities demonstrated in both rodent PD model and HFD-CCl4 model and is currently in clinical development in patients with NASH in phase II.
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Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Receptores Citoplasmáticos y Nucleares , Ácidos y Sales Biliares , Inflamación , Relación Estructura-ActividadRESUMEN
Circular RNAs (circRNAs) play critical roles in clear cell renal cell carcinoma (ccRCC). However, their involvement in sunitinib resistance remains largely unknown. Herein, we identified a novel circRNA, named circME1, which contributes to sunitinib resistance development in ccRCC. CircME1 also promoted proliferation, migration, and invasion of ccRCC cells. Further mechanism analysis showed that circME1 interacted with U1 snRNP at the promoter of its parental gene ME1, thereby upregulating the expression of ME1, enhancing aerobic glycolysis of ccRCC, and promoting its malignant phenotype. Furthermore, ME1 specific inhibitor could effectively repress the oncogenic functions of circME1. Taken together, our study demonstrates that the circME1/ME1 pathway is involved in ccRCC progression and sunitinib resistance development, which may be exploited for anticancer therapy.
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Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glucólisis/genética , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , ARN Circular , Sunitinib/farmacologíaRESUMEN
In vitro production of functional gametes can revolutionize reproduction by reducing generation intervals and accelerating genetic breeding in aquaculture, especially in fish with relatively long generations. Nevertheless, functional sperm production from in vitro-cultured spermatogonia remains a challenge in most aquaculture fish. In this study, we isolated and characterized premeiotic spermatogonia from marine four-eyed sleepers ( Bostrychus sinensis), which are prone to ovotesticular or sterile testicular development, and induced the differentiation of the spermatogonia into flagellated sperm in a three-dimensional (3D) culture system. Artificial insemination indicated that the in vitro-derived sperm were capable of fertilizing mature oocytes to develop into normal larvae. Furthermore, melatonin significantly promoted spermatogonia proliferation and differentiation through the ERK1/2 signaling pathway, and thus increased the efficiency in functional sperm production. The 3D culture system and resulting functional sperm hold great promise for improving the genetic breeding of aquaculture fish.
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Perciformes , Espermatogonias , Animales , Acuicultura , Masculino , Espermatogonias/metabolismo , Espermatozoides , Testículo/metabolismoRESUMEN
To optimize the extraction of polysaccharides from coix seeds (CSP), an auxiliary method of ultrasound was developed by response surface methodology (RSM). The maximum extraction yield (8.340%) was obtained under 480 W power, 16 min ultrasound extraction (UE) time and 21.00 mL/g water to raw material ratio. Compared to hot water extraction (HE), UE-treated CSP led to a higher extraction efficiency and decreased average CSP molecular weight. FT-IR indicated that CSP extracted by UE and HE were neutral polysaccharides, and linkages between sugar units were mainly in the α-conformation. Furthermore, NMR spectra indicated that UE-treated CSP was a neutral polysaccharide with (1 â 6)-linked α-d-glucopyranose in the main chain. Two polysaccharide components (CSP-A and CSP-B) were purified by anion exchange chromatography, therein, CSP-A was more resistant to the digestion in stomach and intestine. These results suggest that CSP-A has the potential to be a functional agent utilized by gut microbes.
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Coix , Antioxidantes , Peso Molecular , Polisacáridos , Espectroscopía Infrarroja por Transformada de Fourier , UltrasonidoRESUMEN
CONTEXT: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. OBJECTIVE: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. DESIGN AND METHODS: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. RESULTS: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 µM). CONCLUSIONS: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.
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Densidad Ósea/fisiología , Ácidos Láuricos/sangre , Osteoporosis Posmenopáusica/diagnóstico por imagen , Posmenopausia/sangre , Absorciometría de Fotón , Adulto , Animales , Biomarcadores/sangre , Línea Celular , China , Estudios Transversales , Femenino , Humanos , Metaboloma , Ratones , Persona de Mediana Edad , Osteogénesis/fisiología , Osteoporosis Posmenopáusica/sangreRESUMEN
Poor postoperative pain (POP) control increases perioperative morbidity, prolongs hospitalization days, and causes chronic pain. However, the specific mechanism(s) underlying POP is unclear and the identification of optimal perioperative treatment remains elusive. Akt and mammalian target of rapamycin (mTOR) are expressed in the spinal cord, dorsal root ganglion, and sensory axons. In this study, we explored the role of Akt and mTOR in pain-related behaviors induced by plantar incision in mice. Plantar incision activated spinal Akt and mTOR in a dose-dependent manner. Pre-treatment with Akt inhibitors intrathecally prevented the activation of mTOR dose-dependently. In addition, blocking the Akt-mTOR signaling cascade attenuated pain-related behaviors and spinal Fos protein expression induced by plantar incision. Our observations demonstrate that Akt-mTOR might be a potential therapeutic target for the treatment of POP.
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DDR1 is considered as a promising target for cancer therapy, and selective inhibitors against DDR1 over other kinases may be considered as promising therapeutic agents. Herein, we have identified a series of 3'-(imidazo[1,2-a]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as novel selective DDR1 inhibitors. Among these, compound 8v potently inhibited DDR1 with an IC50 of 23.8 nM, while it showed less inhibitory activity against DDR2 (IC50 = 1740 nM) and negligible activities against Bcr-Abl (IC50 > 10 µM) and c-Kit (IC50 > 10 µM). 8v also exhibited excellent selectivity in a KINOMEscan screening platform with 468 kinases. This compound dose-dependently suppressed NSCLC cell tumorigenicity, migration, and invasion. Collectively, these studies support its potential application for treatment of NSCLC.
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BACKGROUND: Postoperative pain (POP) is a severe acute pain encountered in patients suffering from an operation, and is less than adequately controlled by the currently available analgesics. Phosphatidylinositol 3-kinase (PI3K) has been reported to have an important role in neuropathic and inflammatory pain. Our previous research revealed that pre-surgical inhibition of spinal PI3K alleviated the pain behavior induced by plantar incision in mice. The aim of this study was to clarify whether post-surgical inhibition of PI3K would attenuate the POP and the underlying mechanisms. METHODS: A POP model was established by plantar incision in Kunming mice. A behavioral test was performed to determine mechanical allodynia, thermal hyperalgesia, and cumulative pain scores. The spinal Fos was detected by immunohistochemistry. The spinal expression of protein kinase B (Akt) or phosphorylated Akt (pAkt) was explored using western blot. The cellular location of pAkt was determined by immunofluorescence. RESULTS: Post-surgical inhibition of PI3K attenuated mechanical allodynia, thermal hyperalgesia, and cumulative pain scores induced by plantar incision significantly in male mice, and mildly in female mice. Post-surgical inhibition of PI3K attenuated the expression of spinal Fos in male mice. Plantar incision induced a time-dependent expression of spinal pAkt in male mice, which was primarily expressed in the spinal dorsal horn, and localized with the neuron and microglia's marker. Post-surgical inhibition of PI3K attenuated the activation of Akt induced by plantar incision in male mice as well. CONCLUSIONS: We concluded that post-surgical inhibition of PI3K could attenuate the pain-related behaviors induced by plantar incision, by suppressing the activation of spinal Akt in male mice. This finding might be used in clinical studies to reach a better understanding of POP mechanisms and optimal treatment.
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Cromonas/farmacología , Hiperalgesia/fisiopatología , Morfolinas/farmacología , Dolor Postoperatorio/prevención & control , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Wortmanina/farmacología , Animales , Femenino , Traumatismos de los Pies/complicaciones , Hiperalgesia/complicaciones , Hiperalgesia/prevención & control , Masculino , Ratones , Dimensión del Dolor/efectos de los fármacos , Dolor Postoperatorio/complicaciones , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Caracteres Sexuales , Médula Espinal/metabolismoRESUMEN
Jumonji domain-containing protein 6 (JMJD6) is a homolog of hypoxia-inducible factor (HIF) asparaginyl hydroxylase, an inhibitor of HIF. HIF-1α is known to participate in neuropathic pain (NPP) during chronic constriction injury (CCI); however, the roles of JMJD6 in NPP have not been systematically investigated. In this study, we examined the temporal distribution and cellular location of JMJD6 in the spinal cord during CCI. In addition, we assessed behavioral changes representative of NPP in rats. Following CCI, lentiviral vectors (LV-JMJD6) were intrathecally administered to observe the changes in the expression of JMJD6, HIF-1α, and its downstream factor caspase-3. Co-immunoprecipitation was used to detect potential interactions between JMJD6 and HIF-1α. We found that JMJD6 was decreased in rats following CCI, which was accompanied by significant NPP-associated behavioral changes. JMJD6 was mainly expressed in neurons. Intrathecal injection of LV-JMJD6 following CCI alleviated the thermal and mechanical hyperalgesia, normalized JMJD6 protein expression, and decreased HIF-1α protein expression with a corresponding reduction in caspase-3 protein expression. Furthermore, the co-immunoprecipitation analyses showed that JMJD6 and HIF-1α protein immunoprecipitated with each other, indicating an interaction between these two proteins. Taken together, the results suggest that JMJD6 may serve as a sensor in neurons of the adult rat spinal cord during the CCI state. Furthermore, JMJD6 may exert its function in NPP by regulating HIF-1α in rats exposed to CCI.
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Treatment of neuropathic pain (NPP) continues to be a major challenge, and the underlying mechanisms remain to be elucidated. Previous studies have demonstrated that histone methylation is important in synaptic plasticity of the nervous system and may affect nuclear factorκB (NFκB) signaling through epigenetic mechanisms. The present study aimed to investigate the role of Jumonji C domain 6 (JMJD6), a histone demethylase, in a chronic constriction injury (CCI) model of NPP. On the third day postCCI surgery, a JMJD6 overexpressing lentiviral vector (LVJMJD6) was intrathecally injected in the rats. Mechanical withdrawal threshold and thermal withdrawal latency were assessed prior surgery and on days 3, 7, 10 and 14 postCCI. The results showed that intrathecal injection with the LVJMJD6 attenuated CCIinduced pain facilitation. The expression of JMJD6 was lower following CCI surgery, and its expression was significantly increased following intrathecal injection with LVJMJD6, compared with levels in normal saline (NS) and negative control lentiviral vector (NC)treated rats. The expression of spinal NFκB phosphorylated (p)p65 subunit and its downstream painassociated effectors, including interleukin 1ß (IL1ß), tumor necrosis factorα (TNFα) and vascular endothelial growth factor (VEGF), were increased following CCI surgery. Intrathecal injection with LVJMJD6 suppressed activation of the pp65 subunit in CCI rats. In addition, expression levels of its downstream effectors IL1ß, TNFα and VEGF were attenuated by intrathecal treatment with LVJMJD6, compared with those in the NS and NCtreated CCI rats. Furthermore, the JMJD6 and p65immunoreactive cells overlapped in the spinal dorsal horn, however, coimmunoprecipitation showed that JMJD6 and the NFκB p65 subunit did not directly interact, indicating other functional connections may exist between these factors following CCI surgery. Collectively, these findings indicated an important mechanism underlying the pathogenesis of NPP. JMJD6 may exert its therapeutic function in NPP by regulating NFκB following CCI.
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Histona Demetilasas con Dominio de Jumonji/metabolismo , FN-kappa B/metabolismo , Neuralgia/complicaciones , Neuralgia/enzimología , Traumatismos de los Nervios Periféricos/complicaciones , Traumatismos de los Nervios Periféricos/enzimología , Animales , Conducta Animal , Enfermedad Crónica , Constricción Patológica , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Inyecciones Espinales , Lentivirus/metabolismo , Masculino , Modelos Biológicos , Neuralgia/patología , Unión Proteica , Subunidades de Proteína/metabolismo , Ratas Sprague-Dawley , Asta Dorsal de la Médula Espinal/metabolismo , Asta Dorsal de la Médula Espinal/patología , Transfección , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
OBJECTIVE: To evaluate the effects of special prescription comment model intervention on prophylactic application of antibiotics during perioperative period of clean operation in our hospital. METHODS: By founding specialist group and prescription comment group, formulating unified form for evaluating prophylactic application of antibiotics during perioperative period of clean operation, establishing comment criteria referring to Guidelines for Clinical Antibiotics Use (2015 edition), Notice on Further Strengthening the Management of Clinical Antibiotics Use, drug package inserts and so on; havivg the aid of administrative intervention and quality assessment, The special prescription comment model was established. Based on stratified sampling (according to the clinical departments, kind of procedure), Each 180 medical records were collected from our hospital during Jan. -Jun. 2015 (before intervention) and Jan. -Jun. 2016 (after intervention). The unified form for perioperative period of clean operation was formulated to comment each medical record in respects of prophylactic utilization rate of antibiotics, medication indication, medication timing, drug selection, usage and dosage, medication course, drug combination, etc. RESULTS: After the following intervention measures were adopted, such as The prophylactic utilization rate of antibiotics of our hospital during perioperative period of clean operation decreased from 96. 7% before intervention to 25. 0% after intervention (P< 0. 05). The rates of drug use without indication, irrational medication timing before surgery, irrational drug selection, irrational usage and dosage, irrational medication course and irrational drug combination were decreased from 71. 3%, 72. 4%, 65. 5%, 23. 0%, 97. 1%, 17. 8% before intervention to 4. 4%, 0, 8. 9%, 11. 1%, 22. 2%, 0 after intervention (P<0. 05) respectively. Before intervention, 8 categories 20 kinds of antibiotics were used prophylactically in our hospital during perioperative period of clean operation; 86 patients used 2 kinds of or more antibiotics, among which there were 31 cases of drug combination and 55 cases of drug replacement. After intervention, 3 categories 4 kinds of antibiotics were used prophylactically in our hospital during perioperative period of clean operation; there was no drug combination and drug replacement. CONCLUSIONS: Special prescription comment model can obviously improve rational use of antibiotics during perioperative period of clean operation.
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A series of 2-aminopyrimidine derivatives were designed and synthesized as highly selective FGFR4 inhibitors. One of the most promising compounds 2n tightly bound FGFR4 with a Kd value of 3.3 nM and potently inhibited its enzymatic activity with an IC50 value of 2.6 nM, but completely spared FGFR1/2/3. The compound selectively suppressed proliferation of breast cancer cells harboring dysregulated FGFR4 signaling with an IC50 value of 0.38 µM. Furthermore, 2n exhibited extraordinary target specificity in a Kinome-wide screen against 468 kinases, with S(35) and S(10) selectivity scores of 0.01 and 0.007 at 1.0 µM, respectively.
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OBJECTIVE:To prepare paeonol-HP-β-cyclodextrin (PAE-HP-β-CD) inclusion compound and to optimize its pre-scription technology. METHODS:PAE-HP-β-CD was prepared by freeze drying method and validated. Using inclusion rate as in-dex,main drug-accessory ratio,inclusion time,inclusion temperature and stirring speed as factors,the preparation technology was optimized by central composite design-response surface methodology. RESULTS:Prepared PAE-HP-β-CD underwent phase transfor-mation. The optimal inclusion technology was as follows as main drug-accessory ratio of 3.39∶1,inclusion temperature of 50 ℃, inclusion time of 3.2 h, stirring speed of 350 r/min. Relative error between measured value (87.46%) and predicted value (89.12%) of inclusion rate was 1.86%(n=6). CONCLUSIONS:PAE-HP-β-CD inclusion compound is prepared successfully, and its prescription technology is stable and feasible.
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OBJECTIVE:To investigate the role of clinical pharmacists on drug therapy for acute exacerbations of chronic ob-structive pulmonary disease(AECOPD)patients with benign prostatic hyperplasia(BPH). METHODS:Clinical pharmacists partici-pated in drug therapy for a AECOPD patient with BPH. According to clinical guideline and relevant literatures,based on the history of disease,the characteristics of bronchodilators and the symptoms of acute urinary retention,it was suggested to stop taking Ip-ratropium bromide solution for inhalation but receive Finasteride capsules 5 mg,po,qd,to reduce prostate volume and improve ob-struction+Terazosin hydrochloride tablets 2 mg,po,qd,to relax urethral smooth muscle;the occurrence of ADR was monitored closely. Salmeterol xinafoate and fluticasone propionate powder for inhalation was suggested and medication guidance for patients af-ter discharge was given by clinical pharmacists. RESULTS:Physicians adopted some suggestions of clinical pharmacists. The pa-tient was stable and had no dysuria. The patient was allowed to leave the hospital with drugs. CONCLUSIONS:Rational use of bronchodilators is directly related to the remission of clinical symptoms and prognosis in AECOPD patients. In view of patient's dis-ease history,drug characteristics and clinical symptoms,clinical pharmacists point to possible risks of anticholinergics use,and as-sist physicians to formulate and adjust therapy plan so as to guarantee the safety and effectiveness of drug use.
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The structure-based design of 1, 2, 3, 4-tetrahydroisoquinoline derivatives as selective DDR1 inhibitors is reported. One of the representative compounds, 6j, binds to DDR1 with a Kd value of 4.7 nM and suppresses its kinase activity with an IC50 value of 9.4 nM, but it is significantly less potent for a panel of 400 nonmutated kinases. 6j also demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model.
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Receptor con Dominio Discoidina 1/antagonistas & inhibidores , Diseño de Fármacos , Isoquinolinas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Administración Oral , Animales , Bleomicina , Receptor con Dominio Discoidina 1/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Isoquinolinas/administración & dosificación , Isoquinolinas/química , Ratones , Modelos Moleculares , Estructura Molecular , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/uso terapéutico , Fibrosis Pulmonar/inducido químicamente , Relación Estructura-ActividadRESUMEN
BACKGROUND: Vasculogenic mimicry (VM), a new pattern of tumor microcirculation system, has been proved to be important for tumor growth and progression and may be one of the causes of antiangiogenesis resistance. Matrix metalloproteinase-9 (MMP9) was shown to correlate with VM formation in some other cancers. However, the relationship between VM formation and MMP9 in renal cell carcinoma (RCC) has not been determined. METHODS: The VM formation and MMP9 expressions were analyzed by CD34/periodic acid-Schiff dual staining and immunohistochemistry in 119 RCC specimens. We used a well-established 3-dimention culture model to compare VM formation in 786-O, 769-P, and HK-2 cell lines in vitro. MMP9 expressions on either messenger RNA or protein levels were compared among the cell lines by quantitative polymerase chain reaction or Western blot. To determine further the relationship between MMP9 and VM in RCC, 786-O and 769-P were treated with specific MMP9 inhibitor or small interfering RNA. VM formation, cell migration, and invasion were subsequently assessed by 3-dimention culture, wound-healing, and transwell assays. RESULTS: Immunohistochemistry demonstrated both VM formation and MMP9 overexpression were positively associated with clinical staging, pathological grade, and metastasis (P<0.01). VM formation was closely correlated with MMP9 overexpression in RCC (r = 0.602, P<0.01). Lower MMP9 expression level was observed in normal kidney cell line HK-2, which was unable to form VM on Matrigel, whereas higher expression of MMP9 was found in VM-forming cancer cell lines 786-O and 769-P. Inhibition of MMP9 not only disrupted VM formation in 786-O and 769-P but also reduced cell migration and invasion. CONCLUSIONS: These results indicate an intimate relationship between MMP9 overexpression and VM formation in RCC. Treatments targeting VM formation by inhibiting the activity of MMP9 could be beneficial in RCC therapy.
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Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Neovascularización Patológica/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Carcinoma de Células Renales/irrigación sanguínea , Carcinoma de Células Renales/enzimología , Línea Celular Tumoral , Niño , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/enzimología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/enzimología , Reacción en Cadena de la Polimerasa , Adulto JovenRESUMEN
OBJECTIVE:To investigate the characteristics and factors of ADR caused by Chinese patent medicine(CPM)and to provide reference for rational drug use and safety evaluation in the clinic. METHODS:158 cases of ADR caused by CPM collect-ed from our hospital during Jan.2009-Dec.2014 were analyzed. RESULTS:The occurrence of ADR caused by CPM was related to patient’s age,route of administration,category of drugs,irrational drug-use and so on. The incidence of ADR in patients over the age of 60 was the highest (31.01%),the largest number of ADR were caused by intravenous injection (79.11%),ADRs were most likely caused by blood-regulating preparation and dissipate blood stasis preparation (79.75%);ADR manifested as lesion of skin and its appendents(43.01%),followed by gastro-intestinal injury(16.06%)and whole-general injury(10.36%). The severe ADR was anaphylactoid reaction;after symptomatic treatment,the prognosis is good. CONCLUSIONS:According to syndrome differentiation and individual difference,CPM should be used rationally,and great importance should be attached to drug use moni-toring to reduce the incidence of ADR.
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OBJECTIVE: To conduct a meta-analysis of the literature evaluating comparisons on the peri-operative and oncological outcomes between laparoscopic partial nephrectomy (LPN) and laparoscopic ablation therapy (LAT) in the treatment of small renal masses (SRMs). MATERIAL AND METHODS: MEDLINE, EMBASE, Google Scholar, Cochrane Library, and CNKI were searched for clinical trials comparing LPN with LAT. Data of peri-operative and follow-up outcomes were extracted and compared. Publication bias was identified and sensitivity analysis was also performed. RESULTS: Data from 11 studies including 928 patients (525 patients in the LPN group and 403 in the LAT group) were collected. Baseline characteristics were compared and differences were found in age, preoperative renal function and proportion of solitary kidney (p < 0.05 respectively). For peri-operative outcomes, the LPN group had greater estimated blood loss, longer operative duration and length of hospital stay, and more peri-operative complications (p < 0.05, respectively). The LAT group had a significantly higher local recurrence (p < 0.05). There was no significant difference in postoperative change of renal function (p = 0.21). CONCLUSION: In comparison with LPN, LAT provides better peri-operative outcomes, but a higher local recurrence rate. LAT does not seem to provide an obvious advantage in protecting renal function. Further clinical trials with randomized design and long-term follow-up are needed.
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Técnicas de Ablación/métodos , Neoplasias Renales/cirugía , Laparoscopía/métodos , Nefrectomía/métodos , Ensayos Clínicos como Asunto , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Recurrencia Local de Neoplasia , Nefrectomía/efectos adversos , Periodo Perioperatorio/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiologíaRESUMEN
<p><b>OBJECTIVE</b>To explore the occupational and reproductive health problems of migrant female workers in electron factory.</p><p><b>METHODS</b>A total number of 2000 female migrant workers were randomly sampled from three electronic factories for the study. All were investigated by questionnaire and data were input to EpiData 3.0 data base, SPSS17.0 statistical software and analyzed by Chi-square test.</p><p><b>RESULTS</b>1971 complete questionnaires were received, the recovery rate reached over 98.6%. The average age of interviewees is (21.1 ± 3.9) years. Junior employee between 16 and 18 years accounted for 19.04%. The average working age was (1.1 ± 2.2) years and about 90% were single including 0.11% of them were divorced. The main occupational hazards were: sodium hydroxide, sodium carbonate, formaldehyde, hydrochloric acid, stannic anhydride, benzene analogues, n-hexane methanol, glycol isopropanol, sulphuric acid, nitric oxide, noise, ultraviolet radiation, etc. Workplace monitoring indicated that benzene and noise levels and ultraviolet radiation were over the national OEL at fewer worksites. More than 50% female workers worked over 8 hours per day and 83% of them worked 22 days per month. The ergonomic problems: 63.86% of them worked with tedious repetitiveness and monotonous job task. About 42% of them need to be continuously with standing posture. As a consequence, there were 30% workers complain about LBP, 21% had experienced work injury; 15% ∼ 18% had some non-specific discomfort, such as insomnia, dysacusis, dizzy and headache. The incidence rate of reproductive system such as abnormal menstrual cycle (5.71%), dysmenorrhea (25.11%), congestion (8.91%), etc. The first four reproductive system disease were pelvic inflammation, adnexitis, cervical erosion, and vaginitis. There are significant differences between continuous and temporary standing work, and repeated and unrepeated job action in terms of dysmenorrheal and congestion related-discomfort(P < 0.05).</p><p><b>CONCLUSION</b>There are many occupational hazards in electronic industry. And there is somewhat a serious occupational and reproductive health problems among female migrant workers, that seem to be a matter of great concern.</p>