RESUMEN
Castration-resistant prostate cancer (CRPC), especially metastatic castration-resistant prostate cancer (mCRPC) is one of the most prevalent malignancies and main cause of cancer-related death among men in the world. In addition, it is very difficult for clinical treatment because of the natural or acquired drug resistance of CRPC. Mechanisms of drug resistance are extremely complicated and how to overcome it remains an urgent clinical problem to be solved. Thus, a comprehensive and thorough understanding for mechanisms of drug resistance in mCRPC is indispensable to develop novel and better therapeutic strategies. In this review, we aim to review new insight of the treatment of mCRPC and elucidate mechanisms governing resistance to new drugs: taxanes, androgen receptor signaling inhibitors (ARSIs) and poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Most importantly, in order to improve efficacy of these drugs, strategies of overcoming drug resistance are also discussed based on their mechanisms respectively.
Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Resistencia a Antineoplásicos , Taxoides , Transducción de SeñalRESUMEN
The wheat aphid Sitobion miscanthi is a dominant and destructive pest in agricultural production. Insecticides are the main substances used for effective control of wheat aphids. However, their extensive application has caused severe resistance of wheat aphids to some insecticides; therefore, exploring resistance mechanisms is essential for wheat aphid management. In the present study, CYP6CY2, a new P450 gene, was isolated and overexpressed in the imidacloprid-resistant strain (SM-R) compared to the imidacloprid-susceptible strain (SM-S). The increased sensitivity of S. miscanthi to imidacloprid after knockdown of CYP6CY2 indicates that it could be associated with imidacloprid resistance. Subsequently, the posttranscriptional regulation of CYP6CY2 in the 3' UTR by miR-3037 was confirmed, and CYP6CY2 participated in imidacloprid resistance. This finding is critical for determining the role of P450 in relation to the resistance of S. miscanthi to imidacloprid. It is of great significance to understand this regulatory mechanism of P450 expression in the resistance of S. miscanthi to neonicotinoids.
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Áfidos , Sistema Enzimático del Citocromo P-450 , Resistencia a los Insecticidas , Insecticidas , MicroARNs , Neonicotinoides , Nitrocompuestos , Neonicotinoides/farmacología , Nitrocompuestos/farmacología , Animales , Insecticidas/farmacología , Resistencia a los Insecticidas/genética , Áfidos/genética , Áfidos/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Imidazoles/farmacologíaRESUMEN
STUDY QUESTION: Does the transplantation of adipose-derived stem cells (ADSCs) on soluble collagen scaffolds (collagen/ADSCs) have better therapeutic effect than transplantation of ADSCs alone, to treat premature ovarian insufficiency (POI) in a rat model induced by Tripterygium Glycosides (TG)? SUMMARY ANSWER: The transplantation of collagen/ADSCs increased the short-term retention of ADSCs in ovaries and contributed to long-term restoration of ovarian function, as well as the fertility of rats with TG-induced ovarian damage. WHAT IS KNOWN ALREADY: About 50% of young women in China, who have been treated with TG, have subsequently developed ovarian insufficiency. Rats exhibit similar symptoms to these patients when given an equivalent dose of TG. Transplantation of ADSCs improves ovarian function impaired by chemotherapy in rodent models. STUDY DESIGN, SIZE, DURATION: After the administration of TG, 54 POI model rats were randomly assigned to 4 groups: phosphate buffered saline (PBS) ( ITALIC! n = 14), collagen ( ITALIC! n = 11), ADSCs ( ITALIC! n = 16) and collagen/ADSCs ( ITALIC! n = 13). Seventeen normal rats were assigned as control group. The retention of ADSCs in ovaries was confirmed immediately or at 3, 7, 14 and 28 days after transplantation ( ITALIC! n = 9). Four weeks after transplantation, ovarian function was evaluated from estrous cycle, estradiol level, the follicle number, granulosa cell proliferation and a fertility test. PARTICIPANTS/MATERIALS, SETTING, METHODS: To establish the POI model, rats were administered 60 mg TG/kg/day intragastrically for 50 days. The estrous cycles were assessed by vaginal smear. The concentration of plasma estradiol in diestrus stage was measured using a radioimmunoassay kit. Disordered estrous cycles and low serum estradiol levels indicated the successful establishment of the POI model. Four types of suspensions (PBS, collagen, ADSCs and collagen/ADSCs) were transplanted directly into the core of the ovaries. The short-term retention of ADSCs in ovaries was evaluated by small-animal positron emission tomography images immediately after transplantation of (18)F-Fluorodeoxyglucose ((18)F-FDG) labeled ADSCs. The long-term retention of ADSCs in ovaries was observed by immunohistochemistry after transplantation of green fluorescent protein (GFP)-labeled ADSCs. Serial sections of ovaries were prepared for histological analysis, follicle counting, and immunohistochemistry for Ki67 and Cleaved-Caspase-3. For the assessment of fertility, rats were mated with proven fertile male rats for 10 days. MAIN RESULTS AND THE ROLE OF CHANCE: The (18)F-FDG signal decreased more slowly in ovaries injected with collagen/ADSCs than in ovaries with injected with ADSCs alone. Significantly more GFP-positive cells were observed in ovaries injected with collagen/GFP-ADSCs than in ovaries injected with GFP-ADSCs alone up to 14 days after the injection. However, in both groups very few GFP-positive cells were present at 4 weeks after transplantation. The collagen/ADSCs and ADSCs groups both showed better estrous cycle recovery than the PBS and collagen groups. The estradiol (E2) level in the collagen/ADSCs group was significantly increased compared with that of the PBS group ( ITALIC! P < 0.05). The number of antral follicles in the collagen/ADSCs group and the ADSCs group significantly increased compared with the PBS group ( ITALIC! P < 0.05). The granulosa cell proliferation in the collagen/ADSCs group was better than in the PBS group ( ITALIC! P < 0.01). The mating rates of the collagen/ADSCs group (88.9%) and the ADSCs group (90.9%) were higher than that of PBS group (60%, ITALIC! P < 0.05). The pregnancy rates of the collagen/ADSCs group (77.8%) and the ADSCs group (72.7%) were higher than the PBS group (50%, ITALIC! P < 0.05). LIMITATIONS, REASONS FOR CAUTION: We chose ADSCs for their accessibility, convenience and safety. We did not use other cells or materials for POI treatments to show that the collagen/ADSCs are the most promising materials. WIDER IMPLICATIONS OF THE FINDINGS: Soluble collagen scaffolds may be useful in stem cells transplantation therapy for POI. STUDY FUNDING/COMPETING INTERESTS: This work is supported by grants from the 'Strategic Priority Research Program' of the Chinese Academy of Sciences (XDA01030000); Maternal-Fetal Medicine from Jiangsu Province Health Department of China (XK2011027); Clinical Center of Obstetric, Gynecologic and Genetic Diseases, Nanjing Health Department of Jiangsu Province, China; Fundamental Research Funds for the Central Universities (20620140652). The authors declare no competing financial interests. TRIAL REGISTRATION NUMBER: Not applicable.
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Preservación de la Fertilidad/métodos , Ovario/fisiología , Insuficiencia Ovárica Primaria/terapia , Trasplante de Células Madre/métodos , Adipocitos , Animales , Técnicas de Cultivo de Célula , Colágeno , Estradiol/sangre , Ciclo Estral , Femenino , Fertilidad , Citometría de Flujo , Inmunohistoquímica , Masculino , Ovario/citología , Ovario/efectos de los fármacos , Tomografía de Emisión de Positrones , Embarazo , Índice de Embarazo , Insuficiencia Ovárica Primaria/inducido químicamente , Ratas , Ratas Sprague-Dawley , Andamios del TejidoRESUMEN
Transplacental infection plays a critical role in the reproductive failure induced by porcine reproductive and respiratory syndrome virus (PRRSV), yet exposure of sows and gilts to classical PRRSV generally leads to reproductive failure after 85 days of gestation. We report, for the first time, that the susceptibility of fetuses to highly pathogenic PRRSV (HP-PRRSV) is similar at 60 days and 90 days of gestation. This difference from classical PRRSV may contribute to its high pathogenicity. A field study of the HP-PRRSV vaccine in pregnant sows at mid-gestation should be considered.
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Intercambio Materno-Fetal , Síndrome Respiratorio y de la Reproducción Porcina/transmisión , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Complicaciones Infecciosas del Embarazo/veterinaria , Animales , Femenino , Feto/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Embarazo , Complicaciones Infecciosas del Embarazo/virología , PorcinosRESUMEN
Imidacloprid is a neonicotinoid insecticide that efficiently controls piercing-sucking mouthparts pests. However, the impact of low lethal concentration of imidacloprid on key demographic parameters of wheat aphids, Schizaphis graminum (R.) and Rhopalosiphum padi (L.) has been scarcely studied. In this study, we used the age stage, two-sex life table approach to investigate the sublethal effects of imidacloprid on the biological traits of S. graminum and R. padi. Bioassays showed that imidacloprid possesses high toxicity to adult S. graminum and R. padi, with LC50 of 3.59 and 13.78 mg L-1 following 24 h exposure. A low lethal concentration of imidacloprid (LC25) significantly decreased adult longevity and total longevity of progeny generation aphids (F1) of S. graminum. Nevertheless, imidacloprid (LC25) had no significant effects on the fecundity and longevity of directly exposed parental parental S. graminum and R. padi (F0). Our results showed that the low lethal concentration of imidacloprid affected the demographic parameters that ultimately impact on the population of S. graminum. This study provides detailed information about the overall effects of imidacloprid on S. graminum and R. padi that might help to manage these two key pests.
Asunto(s)
Áfidos , Insecticidas , Animales , Neonicotinoides/toxicidad , Fertilidad , Insecticidas/toxicidadRESUMEN
Intrauterine growth restriction (IUGR) increases the risk of type 2 diabetes mellitus (T2DM) and metabolic diseases. The pancreas of fetuses with IUGR is usually characterized by pancreatic dysplasia and reduced levels of insulin secretion caused by the diminished replication of ß-cells. Previous studies showed that a low dose of ouabain could reduce the apoptosis of embryonic nephric cells during IUGR and partially restore the number of nephrons at birth. The rescued kidneys functioned well and decreased the prevalence of hypertension. Thus, we hypothesized that ouabain could rescue pancreatic development during IUGR and reduce the morbidity of T2DM and metabolic diseases. Maternal malnutrition was used to induce the IUGR model, and then a low dose of ouabain was administered to rats with IUGR during pregnancy. Throughout the experiment, we monitored the pattern of weight increase and evaluated the metabolic parameters in the offspring in different stages. Male, but not female, offspring in the IUGR group presented catch-up growth. Ouabain could benefit the impaired glucose tolerance of male offspring; however, this desirable effect was eliminated by aging. The insulin sensitivity was significantly impaired in male offspring with IUGR, but it was improved by ouabain, even during old age. However, in the female offspring, low birth weight appeared to be a beneficial factor even in old age; administering ouabain exacerbated these favorable effects. Our data suggested that IUGR influenced glucose metabolism in a sex-specific manner and ouabain treatment during pregnancy exerted strongly contrasting effects in male and female rats.
Asunto(s)
Diabetes Mellitus Tipo 2 , Retardo del Crecimiento Fetal , Embarazo , Femenino , Humanos , Ratas , Animales , Masculino , Retardo del Crecimiento Fetal/metabolismo , Ouabaína/farmacología , Ratas Sprague-Dawley , Diabetes Mellitus Tipo 2/complicaciones , MetabolomaRESUMEN
BACKGROUND: Disruptions of angiogenesis can have a significant effect on the healing of uterine scars. Human endometrial perivascular cells (CD146+PDGFRß+) function as stem cells in the endometrium. Cysteine-rich angiogenic inducer 61 (CYR61) plays an important role in vascular development. The purpose of this study was to observe the effects of the transplantation of human endometrial perivascular cells (En-PSCs) overexpressing CYR61 on structural and functional regeneration in rat models of partial full-thickness uterine excision. METHODS: We first sorted human En-PSCs from endometrial single-cell suspensions by flow cytometry. Human En-PSCs expressing low or high levels of CYR61 were then generated via transfection with a CYR61-specific small interfering ribonucleic acid (si-CYR61) construct or overexpression plasmid. To establish a rat model of uterine injury, a subset of uterine wall was then resected from each uterine horn in experimental animals. Female rats were randomly assigned to five groups, including a sham-operated group and four repair groups that received either PBS loaded on a collagen scaffold (collagen/PBS), En-PSCs loaded on a collagen scaffold (collagen/En-PSCs), En-PSCs with low CYR61 expression loaded on a collagen scaffold (collagen/si-CYR61 En-PSCs), and En-PSCs overexpressing CYR61 loaded on a collagen scaffold (collagen/ov-CYR61 En-PSCs). These indicated constructs were sutured in the injured uterine area to replace the excised segment. On days 30 and 90 after transplantation, a subset of rats in each group was sacrificed, and uterine tissue was recovered and serially sectioned. Hematoxylin and eosin staining and immunohistochemical staining were then performed. Finally, the remaining rats of each group were mated with fertile male rats on day 90 for a 2-week period. RESULTS: Sorted En-PSCs expressed all recognized markers of mesenchymal stem cells (MSCs), including CD10, CD13, CD44, CD73, CD90, and CD105, and exhibited differentiation potential toward adipocytes, osteoblasts, and neuron-like cells. Compared with En-PSCs and En-PSCs with low CYR61 expression, En-PSCs with elevated CYR61 expression enhanced angiogenesis by in vitro co-culture assays. At day 90 after transplantation, blood vessel density in the collagen/ov-CYR61 En-PSCs group (11.667 ± 1.287) was greater than that in the collagen/En-PSCs group (7.167 ± 0.672) (P < 0.05) and the collagen/si-CYR61 En-PSCs group (3.750 ± 0.906) (P < 0.0001). Pregnancy rates differed among groups, from 40% in the collagen/PBS group to 80% in the collagen/En-PSCs group, 12.5% in the collagen/si-CYR61 En-PSCs group, and 80% in the collagen/ov-CYR61 En-PSCs group. In addition, four embryos were evident in the injured uterine horns of the collagen/ov-CYR61 En-PSCs group, while no embryos were identified in the injured uterine horns of the collagen/PBS group. CONCLUSIONS: The results showed that CYR61 plays an important role in angiogenesis. Collagen/ov-CYR61 En-PSCs promoted endometrial and myometrial regeneration and induced neovascular regeneration in injured rat uteri. The pregnancy rate of rats treated with transplantation of collagen/En-PSCs or collagen/ov-CYR61 En-PSCs was improved. Moreover, the number of embryos implantation on the injured area in uterus was increased after transplantation of collagen/ov-CYR61 En-PSCs.
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Proteína 61 Rica en Cisteína/metabolismo , Células Madre Mesenquimatosas/citología , Neovascularización Fisiológica/fisiología , Regeneración/fisiología , Útero/citología , Útero/lesiones , Útero/metabolismo , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Cromatografía Liquida , Colágeno/metabolismo , Proteína 61 Rica en Cisteína/genética , Endometrio/citología , Endometrio/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Fertilidad/genética , Fertilidad/fisiología , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Masculino , Células Madre Mesenquimatosas/metabolismo , Miometrio/citología , Miometrio/metabolismo , Neovascularización Fisiológica/genética , Embarazo , Ratas , Regeneración/genética , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Severe injuries of the uterus may trigger uterine scar formation, ultimately leading to infertility or obstetrical complications. To date, few methods have adequately solved the problem of collagen deposition in uterine scars. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown great promise in clinical applications. The objective of this study was to investigate the effect of a scaffold/UC-MSCs construct on collagen degradation and functional regeneration in rat uterine scars following full-thickness excision of uterine walls. METHODS: In order to establish a rat model of uterine scars, the uterine wall of approximately 1.0 cm in length and 0.5 cm in width (one-third of the uterine circumference) was excised from each uterine horn. A total of 128 scarred uterine horns from 64 rats were randomly assigned to four groups, including a PBS group (n = 32 uterine horns), scaffold group (n = 32 uterine horns), UC-MSCs group (n = 32 uterine horns) and scaffold/UC-MSCs group (n = 32 uterine horns) to investigate the effect of different treatments on the structure and function of uterine scars. PBS, degradable collagen fibres, UC-MSCs or UC-MSCs mixed with gelatinous degradable collagen fibres were injected into four pre-marked points surrounding each uterine scar, respectively. At days 30 and 60 post-transplantation, a subset of rats (n = 8 uterine horns) from each group was euthanized and serial sections of uterine tissues containing the operative region were prepared. Haematoxylin-eosin staining, Masson's trichrome staining, and immunohistochemical staining for MMP-2, MMP-9, α-SMA and vWF were performed. Finally, another subset of rats (n = 16 uterine horns) from each group was mated with male rats at day 60 post-transplantation and euthanized 18 days after the presence of vaginal plugs to check numbers, sizes and weights of fetuses, as well as sites of implantation. RESULTS: The scaffold/UC-MSCs group exhibited obvious collagen degradation compared with the other three groups. At day 60 post-transplantation, the number of MMP-9-positive cells in the scaffold/UC-MSCs group (25.96 ± 3.63) was significantly higher than that in the PBS group (8.19 ± 1.61, P < 0.01), the scaffold group (7.25 ± 2.17, P < 0.01) and the UC-MSCs group (8.31 ± 2.77, P < 0.01). The pregnancy rate in the scaffold/UC-MSCs group (10/16) was also significantly higher than that in the PBS group (2/16, P < 0.017), the scaffold group (1/16, P < 0.017) and the UC-MSCs group (3/16, P < 0.017). CONCLUSIONS: The scaffold/UC-MSCs system facilitated collagen degradation in uterine scars via upregulation of MMP-9, which was secreted by transplanted UC-MSCs, and promoted regeneration of the endometrium, myometrium and blood vessels in uterine scars. Furthermore, the scaffold/UC-MSCs-treated uterine scars showed nearly complete restoration of receptive fertility.
Asunto(s)
Cicatriz Hipertrófica/terapia , Colágeno/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Útero/lesiones , Cicatrización de Heridas , Animales , Femenino , Metaloproteinasa 9 de la Matriz/genética , Células Madre Mesenquimatosas/citología , Proteolisis , Ratas , Ratas Sprague-Dawley , Andamios del Tejido , Regulación hacia Arriba , Útero/metabolismo , Útero/patologíaRESUMEN
BACKGROUND@#Postoperative gastrointestinal dysfunction (PGD) is one of the most common complications in patients undergoing major abdominal surgery. Acupuncture has been used widely in gastrointestinal diseases due to its effectiveness and minimally invasive nature.@*OBJECTIVE@#This study evaluated the efficacy of using transcutaneous electrical acupoint stimulation (TEAS) during the surgery and postoperative recovery in patients with gastric and colorectal surgery for improving postoperative gastrointestinal function.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS@#A total of 280 patients undergoing abdominal surgery were stratified by type of surgery (i.e., gastric or colorectal surgery) and randomly allocated into the TEAS group (group T) or the sham group (group S). Patients in group T received TEAS at LI4, PC6, ST36 and ST37. Patients in group S received pseudo-TEAS at sham acupoints. The stimulation was given from 30 min before anesthesia until the end of surgery. The same treatment was performed at 9 am on the 1st, 2nd and 3rd days after surgery, until the recovery of flatus in patients.@*MAIN OUTCOME MEASURES@#The primary outcome was the time to the first bowel motion, as detected by auscultation. The secondary outcomes included the first flatus and ambulation time, changes of perioperative substance P (SP), incidence of PGD, postoperative pain, postoperative nausea and vomiting (PONV) and some economic indicators.@*RESULTS@#The time to first bowel motion, first flatus and first ambulation in group T was much shorter than that in group S (P < 0.01). In patients undergoing colorectal surgery, the concentration of SP was lower in group T than in group S on the third day after the operation (P < 0.05). The average incidence of PGD in all patients was 25%, and the frequency of PGD was significantly lower in group T than in group S (18.6% vs. 31.4%, respectively; P < 0.05). TEAS treatment (odds ratio = 0.498; 95% confidence interval: 0.232-0.786) and type of surgery were relevant factors for the development of PGD. Postoperative pain score and PONV occurrence were significantly lower in group T (P < 0.01). Postoperative hospitalization days and the resulting cost to patients were greatly reduced in the TEAS group (P < 0.01).@*CONCLUSION@#Perioperative TEAS was able to promote the recovery of postoperative gastrointestinal function, reduce the incidence of PGD and PONV. The concentration of SP was decreased by TEAS treatment, which indicates that the brain-gut axis may play a role in how TEAS regulates gastrointestinal function.@*TRIAL REGISTRATION@#Chinese Clinical Trial Registry, ChiCTR1900023263.
RESUMEN
A variety of diseases may lead to hysterectomies or uterine injuries, which may form a scar and lead to infertility. Due to the limitation of native materials, there are a few effective methods to treat such damages. Tissue engineering combines cell and molecular biology with materials and mechanical engineering to replace or repair damaged organs and tissues. The use of human embryonic stem cells (hESCs) as a donor cell source for the replacement therapy will require the development of simple and reliable cell differentiation protocols. This study aimed at efficiently generating endometrium-like cells from the hESCs and at using these cells with collagen scaffold to repair uterine damage. The hESCs were induced by co-culturing with endometrial stromal cells, and simultaneously added cytokines: epidermal growth factor (EGF), platelet-derived growth factor-b (PDGF-b), and E2. Expression of cell specific markers was analyzed by immunofluorescence and reverse trascription-polymerase chain reaction to monitor the progression toward an endometrium-like cell fate. After differentiation, the majority of cells (>80%) were positive for cytokeratin-7, and the expression of key transcription factors related to endometrial development, such as Wnt4, Wnt7a, Wnt5a, Hoxa11, and factors associated with endometrial epithelial cell function: Hoxa10, Intergrinß3, LIF, ER, and PR were also detected. Then, we established the uterine full-thickness-injury rat models to test cell function in vivo. hESC-derived cells were dropped onto collagen scaffolds and transplanted into the animal model. Twelve weeks after transplantation, we discovered that the hESC-derived cells could survive and recover the structure and function of uterine horns in a rat model of severe uterine damage. The experimental system presented here provides a reliable protocol to produce endometrium-like cells from hESCs. Our results encourage the use of hESCs in cell-replacement therapy for severe uterine damage in future.
Asunto(s)
Colágeno/farmacología , Células Madre Embrionarias/citología , Endometrio/citología , Regeneración/fisiología , Andamios del Tejido/química , Animales , Biomarcadores/metabolismo , Bovinos , Diferenciación Celular/efectos de los fármacos , Línea Celular , Forma de la Célula/efectos de los fármacos , Células Madre Embrionarias/efectos de los fármacos , Endometrio/trasplante , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Ratas Sprague-Dawley , Regeneración/efectos de los fármacosRESUMEN
OBJECTIVE@#To evaluate the efficacy of electro-acupuncture (EA) or transcutaneous electrical acupoint stimulation (TEAS) on perioperative cerebral blood flow (CBF) and neurological function in ischemic stroke (IS) patients undergoing carotid artery stenting (CAS).@*METHODS@#In total, 124 consecutive IS patients were randomly allocated to the EA, TEAS, and sham groups (groups A, T, and S; 41, 42, and 41 cases, respectively) by software-derived random-number sequence. Groups A and T received EA and TEAS, respectively, at the Shuigou (GV 26) and Baihui (GV 20), Hegu (LI4) and Waiguan (TE 5) acupoints. Group S received sham EA. The stimulation was started from 30 min before surgery until the end of the operation. The primary outcome was the CBF at 30 min after surgery, which was measured by transcranial Doppler sonography. The secondary outcomes included hyperperfusion incidence and neurological function. National Institutes of Health Stroke Scale (NIHSS) and General Evaluation Scale (GES) scores were recorded at 1 week, 1 month, and 3 months postoperatively.@*RESULTS@#Mean CBF velocity at 30 min after surgery in groups A and T was much lower than that in Group S (P < 0.05); the incidence of hyperperfusion in Groups A and T was also lower than that in group S (P <0.05). Acupuncture was an independent factor associated with reduced incidence of hyperperfusion (OR=0.042; 95% CI: 0.002-0.785; =0.034). NIHSS and GES scores improved significantly at 1 week postoperatively in Groups A and T than in Group S (P < 0.05). Relative to Group S, groups A and T exhibited significantly lower incidences of moderate pain, as well as higher incidences of satisfaction with anesthesia, at 1 day postoperatively (P < 0.05).@*CONCLUSIONS@#EA or TEAS administered in combination with local anesthesia during CAS can inhibit transient increases in CBF, reduce the incidence of postoperative hyperperfusion, and improve neurological function. (Registration No. ChiCTR-IOR-15007447).
RESUMEN
OBJECTIVE: To establish digitized Virtual Chinese Human Male No.1 (VCH-M1) image dataset with a 0.2-mm equal interval. METHODS: The body of a 24-year-old male was used for this study. Perfusion with phenol and vermilion of the arteries was performed, followed by body shape adjustment by cold saline and pre-embedding with broken ices in an upside-down position, which was completed in a stepwise procedure to minimize body shape deformation. Section milling was conducted subsequently with the section thickness of 2 mm and the section images were captured by digital camera, which were immediately transferred to a computer for storage and processing. RESULTS: A total of 9 232 sections were obtained for the whole body, and the resolution of each of the image in TIF format was 3 024x2 016 pixels, resulting in the size of approximately 18 M for each image and about 161 G for the whole dataset. CONCLUSIONS: Compared with VCH-F1, the image quality in VCH-M1 dataset is significantly improved, demonstrated by much clearer tissue boundary in the images and minimized body shape deformation during the embedding process.
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Anatomía Transversal , Interfaz Usuario-Computador , Adulto , China , Recolección de Datos , Humanos , MasculinoRESUMEN
Manipulations are essential to the acupuncture curative effect. With the technique limited, the researches on acupuncture manipulations can only be carried out with respect to the senses and experience of doctors and patients, thus seriously impeding the modernization and internationalization of acupuncture. Both the modern integration technology of transducer and the biomechanical principles are applied to develop a detection system that can measure the interaction force between the manipulator and the manipulated patient on the needle at each kind of manipulation. Through clinical practice, the force waveforms acting on needle with the manipulations of symmetrical twirling-rotating and symmetrical lifting-inserting were recorded so as to realize the quantitative, objective and real-time detection of the force during the acupuncture process, which provided a new experimentation means and analysis method for the improvement of clinical curative effect and quantitative research of acupuncture and meridians.
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Acupuntura/instrumentación , Técnicas Biosensibles/instrumentación , Agujas , Programas Informáticos , Diseño de Equipo , Humanos , Mecánica , Medicina Tradicional China , Diseño de SoftwareRESUMEN
Serious injuries of endometrium in women of reproductive age are often followed by uterine scar formation and a lack of functional endometrium predisposing to infertility or miscarriage. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown great promise in clinical applications. In the present study, BM-MSCs loaded onto degradable collagen membranes were constructed. Collagen membranes provided 3-dimmensional architecture for the attachment, growth and migration of rat BM-MSCs and did not impair the expression of the stemness genes. We then investigated the effect of collagen/BM-MSCs constructs in the healing of severe uterine injury in rats (partial full thickness uterine excision). At four weeks after the transplantation of collagen/BM-MSCs constructs, BM-MSCs were mainly located to the basal membrane of regenerative endometrium. The wounded tissue adjacent to collagen/BM-MSCs constructs expressed higher level of bFGF, IGF-1, TGFß1 and VEGF than the corresponding tissue in rats receiving collagen construct alone or in spontaneous regeneration group. Moreover, the collagen/BM-MSCs system increased proliferative abilities of uterine endometrial and muscular cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive the embryo and support its development to a viable stage. Our findings indicate that BM-MSCs may support uterine tissue regeneration.
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Colágeno/química , Trasplante de Células Madre Mesenquimatosas/métodos , Ingeniería de Tejidos , Andamios del Tejido , Útero/citología , Útero/lesiones , Animales , Células de la Médula Ósea/metabolismo , Endometrio/metabolismo , Femenino , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratas , Ratas Sprague-Dawley , Regeneración , Factor de Crecimiento Transformador beta1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas/fisiologíaRESUMEN
Serious injuries of uterine which lead to scar formation will finally result in infertility or pregnancy complications. There are few effective methods to treat such damages because of the shortage of native tissues. Vascular endothelial growth factor (VEGF) is important for the formation of new vessels and re-epithelialization of endometrium. Here we produced a collagen-binding VEGF by fusing a collagen-binding domain to the N-terminal of native VEGF. After injection into a rat scarred uterus model (partial of rat uterine horn was excised and left for scar formation) the collagen targeting VEGF promoted remodeling of the scarred uterus including the regeneration of endometrium, muscular cells, and vascularization and improved pregnancy outcomes. Thus, collagen-binding VEGF may be a pragmatic solution for the treatment of severe uterine damages.
Asunto(s)
Colágeno/química , Ingeniería de Tejidos/métodos , Útero/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Línea Celular Tumoral , Cicatriz/patología , Endometrio/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Neovascularización Patológica , Estructura Terciaria de Proteína , Ratas , Ratas Sprague-Dawley , Regeneración , Útero/citología , Cicatrización de HeridasRESUMEN
Severe damages of uterine endometrium which prevent embryos from implantation and placentation finally often result in infertility or pregnant complications. There is lack of effective treatments due to the limitation of native materials available and complexity of the function and internal environment of uterus. In the present study, a collagen targeting basic fibroblast growth factor (bFGF) delivery system was constructed by a collagen membrane loaded with bFGF fused a collagen-binding domain (CBD) to the N-terminal which limits the diffusion of bFGF from collagen. We tested the bFGF delivery system in rats under the severe uterine damage model (partial rat uterine horn excision/reconstruction), and found this delivery system improved regeneration abilities of uterine endometrium and muscular cells, improved vascularization, as well as better pregnancy outcomes in rats. Therefore, this targeting delivery system may be an effective strategy for uterine tissue regeneration.
Asunto(s)
Colágeno/farmacología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Regeneración/efectos de los fármacos , Andamios del Tejido/química , Útero/efectos de los fármacos , Útero/fisiología , Animales , Bovinos , Proliferación Celular/efectos de los fármacos , Colágeno/ultraestructura , Endometrio/irrigación sanguínea , Endometrio/efectos de los fármacos , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Embarazo , Resultado del Embarazo , Unión Proteica/efectos de los fármacos , Ratas , Útero/patología , Útero/cirugía , Factor de von Willebrand/metabolismoRESUMEN
<p><b>OBJECTIVE</b>To observe the impacts of transcutaneous acupoint electric stimulation on hemodynamics, anesthetic and relevant complications in patients of transsphenoidal pituitary tumor resection (TPTR).</p><p><b>METHODS</b>Ninety cases of the selective TPTR were randomized into a transcutaneous acupoint electric stimulation group (group T), a sham-acupoint group (group S) and a control group (group C); 30 cases in each one. In group T, the transcutaneous acupoint electric stimulation at Hegu (LI 4), Waiguan (TE 5), Jinmen (BL 63), Taichong (LR 3), Zusanli (ST 36) and Qiuxu (GB 40). In group S, the transcutaneous acupoint electric stimulation was applied to the sham-acupoints. In group C, the acupoints selected were same as those in group T, but the electrode pads were just attached on the related points with no-electric stimulation. The electric stimulation lasted from analgesic induction till the end of the operation. The endotracheal intubation was done under the induction by propofol, fentanyl and vecuronium bromide. Propofol and remifentanil were maintained till the end of operation. Blood pressure, heart rate, bispectral index (BIS) value, anesthetic and postoperative recovery situation were recorded.</p><p><b>RESULTS</b>The hemodynamics maintained stably in each group. In group T, the mean arterial pressure 1 min after intubation, after extubation and during directional force recovery was all lower than the other two groups respectively (all P<0.05). In group T, the effect-site concentration of fentaryl in the exposure saddle area and tumor removal stage was lower than the other two groups (all P<0.05). In 24 h after operation, 2 cases presented nausea and vomiting in group C. There were no relevant complications in the rest groups.</p><p><b>CONCLUSION</b>The transcutaneous acupoint electric stimulation improves the stability of hemodynamics in perioperative stage, reduces the intraoperative opi oids dosages and improves the quality of anesthetic recovery.</p>
Asunto(s)
Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Analgesia por Acupuntura , Puntos de Acupuntura , Anestesia Intravenosa , Periodo Perioperatorio , Neoplasias Hipofisarias , Cirugía General , Estimulación Eléctrica Transcutánea del NervioRESUMEN
OBJECTIVE: To study the mechanisms of the expression of exogenous gene injected via the mammary duct in rat mammary gland tissue. METHODS: Thirty-six SD rats were grouped according to the stages of mammary growth (9 weeks after birth, 7, 12 and 18 days of pregnancy, and 7 and 14 days post partum, 6 rats in each stage). pCE-29 plasmid for highly efficient expression of green fluorescent protein (GFP) and in vivo jetPEITM were mixed and injected into the 5th pair of the mammary glands via the mammary ducts in each rat. The mammary glands were taken to prepare freezing slices 48 h after the injection and observed under fluorescence microscope. HE staining was performed for slices with GFP expression to locate the site of GFP expression by comparison of the images before and after staining. Paraffin sections of the mammary glands with HE staining were also obtained from normal rats in different stages of mammary development. RESULTS: After pCE-29 plasmid injection, GFP expression was observed in the mammary glands of 2 rats in pregnancy day 12 group and in postpartum day 7 group. The green spots shown by fluorescence microscopy were found in the mammary epithelial cells after image comparison. The gland cells undergoing cell division were more numerous in the two stages (pregnancy day 12 and postpartum day 7) than in other stages of mammary development. CONCLUSIONS: In the two stages of pregnancy day 12 and postpartum day 7, exogenous genes injected via the mammary duct can be expressed in the mammary glands. In these stages, the stem cells in the mammary gland epithelia differentiate continuously and the mammary gland epithelial cells flourish under the regulation by hormones to allow better chance for exogenous gene acceptance in the context of active DNA replication in the gland cells. This finding provides important experimental evidence for further studies of mammary gland bioreactor in animals.
Asunto(s)
Proteínas Fluorescentes Verdes/metabolismo , Glándulas Mamarias Animales/metabolismo , Plásmidos/genética , Animales , Femenino , Técnicas de Transferencia de Gen , Proteínas Fluorescentes Verdes/genética , Histocitoquímica , Inyecciones , Microscopía Fluorescente , Plásmidos/administración & dosificación , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>To observe the effects of electro-acupuncture combined with sevoflurane anesthesia used in neurosurgery patients and the speed of recovery following surgery.</p><p><b>METHODS</b>Eighty patients with supratentorial tumor resection were anesthetized with sevoflurane and randomly allocated into the complete anesthesia group (Group A) and the electro-acupuncture combined with sevoflurane group (Group B). Han's acupoint nerve stimulator with 2/100 Hz frequency was used to stimulate the points. Patients in Group B received electroacupuncture at Fengchi (GB20) toward Tianzhu (BL10) and Cuanzhu (BL2) toward Yuyao (EX-HN4) at the same side of the craniotomy before anesthesia induction. The stimulation was lasted from anesthesia induction until the end of operation. Patients in Group A were pasted with the conducting wire at the aforesaid points, but with no acupuncture or electric stimulation. All patients were induced with propofol 2 mg/kg, sufentanyl 0.3 microg/kg, and vecuronium 0.1 mg/kg, and maintained anesthesia with 2% sevoflurane. The bispectral index (BIS) was maintained ranging 40 -50. The sevoflurane was stopped inhaling at the end of the operation. The end-tidal sevoflurane concentration, minimum alveolar concentration (MAC), BIS, and the anesthesia recovery at each time point were recorded in the two groups.</p><p><b>RESULTS</b>There was no statistical difference in the mean arterial pressure or the heart rate. The end-tidal concentration and MAC of sevoflurane were significantly lower in Group B than in Group A at each time point (P<0.05). The dose of sevoflurane was reduced by 8.34% +/- 1.24% in Group B when compared with that of Group A. The BIS value could be maintained ranging 40 - 50 in both groups, thus guaranteeing the anesthesia depth. The time for the spontaneous respiration recovery, the extubation time, the time for opening eyes, the time for the voluntary movement recovery, and the time for orientation recovery, and the time for leaving the operation room were significantly shorter in Group B than in Group A (P<0.01). The occurrence of dysphoria, nausea and vomiting was less in Group B than in Group A.</p><p><b>CONCLUSIONS</b>Electro-acupuncture combined with sevoflurane used in neurosurgery could save the dose of sevoflurane, significantly shorten the anesthesia recovery time, and improve the quality of the anesthesia recovery. It was a favorable anesthesia method.</p>
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anestesia , Métodos , Electroacupuntura , Éteres Metílicos , Usos Terapéuticos , Neurocirugia , Métodos , Neoplasias Supratentoriales , Cirugía GeneralRESUMEN
<p><b>OBJECTIVE</b>To observe the supplementary analgesic effect of electroacupuncture and its influence on the maintenance of anesthesia and the speed of recovery of patients undergoing craniotomy.</p><p><b>METHODS</b>Eighty cases of supratentorial tumor resection were randomly divided into group A and group S, 40 cases in each group. All the patients were anesthetized with 2% Sevoflurane. The patients in group A received electroacupuncture at Hegu (LI 4) and Waiguan (TE 5), Jinmen (BL 63) and Taichong (LR 3), Zusanli (ST 36) and Qiuxu (GB 40) from anesthesia beginning to the end of operation, and in group S without electroacupuncture. The end-tidal Sevoflurane concentration, minimum alveolar concentration (MAC), bispectral index (BIS) and the information during anesthesia recovery stage were recorded, respectively.</p><p><b>RESULTS</b>The end-tidal concentration and MAC of Sevoflurane in group A at all times were significant lower than those in group S (P<0.05, P<0.01) with a Sevoflurane saving of 9.62% on average. The BIS in group A during a few phases were higher than that in group S (all P<0.05). During anesthesia recovery stage, the time of each phase in group A was significantly shorter than that in group S (all P<0.01). No dysphoria and one case with nausea and vomiting were shown in group A, but in group S, 2 patients had dysphoria and 3 patients had nausea and vomiting.</p><p><b>CONCLUSION</b>Electroacupuncture combined with Sevoflurane anesthesia can decrease the dosage of Sevoflurane, shorten the recovery time of anesthesia and improve the quality of anesthesia recovery of the patients undergoing resection of supratentorial tumor.</p>