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Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
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Humanos , Bencidamina , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Fosforilación , Proliferación Celular , Línea Celular Tumoral , Apoptosis , Quinasa 2 Dependiente de la CiclinaRESUMEN
Ischemic stroke is caused by a variety of factors caused by intracerebral artery stenosis or obstruction, can lead to cerebral ischemia, hypoxia, neuronal necrosis and neurological dysfunction and other pathological injuries, with high morbidity, high disability rate, high mortality characteristics. Cerebral ischemia-reperfusion injury is the main secondary injury, which can lead to permanent disability or even death in severe cases. With the development of traditional Chinese medicine(TCM) modernization, the extraction and application of active components of TCM have been paid more and more attention. Salidroside, as the main active component of Rhodirosea, a rare Chinese medicinal herb, has been proved to fight cerebral ischemia injury by inhibiting cell apoptosis, anti-oxidative stress, reducing inflammatory response, protecting blood-brain barrier, regulating autophagy, promoting nerve remodeling and synaptic regeneration in preclinical trials. However, due to its multi-pathway, multi-pathway and multi-target action characteristics, the specific mechanism of salidroside to improve cerebral ischemia injury has not been fully elucidated. By reviewing relevant literature in the past decade, the author reviewed the mechanism of action of salidroside in the treatment of ischemic brain injury, and summarized the recent progress of its pharmacokinetic studies and safety evaluation, in order to provide theoretical basis and new research ideas for the development and clinical application of the active ingredients of traditional Chinese medicine.
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BACKGROUND AND OBJECTIVE: Securing the airway in the surgery of maxillofacial disorders and traumas is fundamental during the operation. The present study aims to investigate the beneficial sedative effects of dexmedetomidine (DEX) in patients who underwent maxillofacial surgery with regional anesthesia compared to general anesthesia. METHODS: Fifty patients, aged 20-45 years old were randomly divided into two groups of regional anesthesia (RA) and general anesthesia (GA) (each n=25). The group RA received regional block with sedation (DEX: 1 µg/kg infused over 10 min followed by the maintenance dose of 0.5 µg/kg/h) and the group GA underwent general anesthesia (DEX: 0.1 µg/kg/min over 10 min followed by 0.4-0.7 µg/kg/h). Postoperative pain scores, anesthesia outcomes, hemodynamic parameters, the time of the post-anesthesia care unit (PACU) discharge and intra and postoperative complications were comparatively assessed in both groups. RESULTS: The baseline characteristics of the patients (age, gender, BMI, and ASA physical status) showed no differences between the two groups (P>0.05). Although the duration of surgery and recovery time showed no differences between the groups, the duration of anesthesia and extubation time was remarkably lower in the RA group than in the GA group (P<0.01). Administration of nerve blocks demonstrated less pain and longer sleep time in the postoperative phase as compared to the GA group. Heart rate and mean arterial blood pressure were significantly less in the RA group at the end of the loading dose of DEX and incision time (P<0.05). SpO2, respiration rate and Ramsay sedation scale did not exhibit any significant differences between the two groups at all-time points (P>0.05). No significant differences were observed with regard to the adverse events between the two groups (P>0.05). CONCLUSIONS: Although our findings revealed that both methods are suitable and safe methods for maxillofacial surgery, the outcomes of anesthesia with regional block and sedation include less pain in the postoperative phase, shorter extubation time and earlier discharge from the PACU demonstrated that this method is more reliable for maxillofacial surgery. Further controlled studies are needed to compare the effectiveness and safety profiles of two RA and GA techniques and also to compare DEX with other anesthetic agents to achieve optimum outcomes in maxillofacial surgeries.
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Anestesia de Conducción , Dexmedetomidina , Cirugía Bucal , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Dexmedetomidina/uso terapéutico , Dexmedetomidina/efectos adversos , Anestesia General/métodos , DolorRESUMEN
Objective:To analyze skin manifestations of pediatric inflammatory bowel disease (IBD) .Methods:Children with IBD were collected from pediatric wards in Peking University Third Hospital from January 2010 to January 2022, and their skin manifestations were retrospectively analyzed.Results:A total of 50 children with IBD were included, including 27 with Crohn′s disease and 23 with ulcerative colitis. Twenty-five (50%) patients had skin manifestations, including specific skin manifestations in 11 (22%) and relevant skin manifestations in 11 (22%) . Specific skin manifestations included cutaneous perianal Crohn′s disease in 2 cases, and anal fistula and/or perianal abscess in 9 cases; relevant skin manifestations included erythema nodosum in 5 cases, aphthous stomatitis in 3 cases, psoriasis in 1 case, polyarteritis nodosa in 1 case, and Henoch-Sch?nlein purpura in 1 case. Compared with the ulcerative colitis group, the Crohn′s disease group was more prone to suffer from specific skin manifestations and relevant skin manifestations, and there were significant differences in the prevalence of specific and relevant skin manifestations between the two groups (both P < 0.05) . Of the 27 children with Crohn′s disease, 19 (70%) had one or more skin manifestations, 2 of whom successively presented with 4 different skin manifestations. One child with Crohn′s disease and 1 with ulcerative colitis had 3 different skin manifestations in different periods. The fecal calprotectin level was elevated in all children with skin manifestations, and in 12 (48%) children without skin manifestations. The skin lesions of 5 children were improved or subsided after dose adjustment (1 case) or switch (4 cases) of biological agents. Conclusions:Half of the children with IBD have skin manifestations, and children with Crohn′s disease are more prone to have specific and relevant skin manifestations. Different skin manifestations could be observed in the same child in different periods. Multidisciplinary teamwork is conducive to the overall control of this disease.
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Cerebral ischemia-reperfusion injury (CIRI) is a further injury of brain tissue after the recovery of blood supply in ischemic stroke, which seriously affects the quality of life of patients. The pathological mechanism of CIRI is complex, mainly involving excitatory amino acid toxicity, apoptosis, inflammation, and oxidative stress. Studies have proved that Chinese herbal medicines and their active components have unique advantages and good application prospects in the prevention and treatment of CIRI. Quercetin is a flavonoid ubiquitous in a variety of Chinese medicinal herbs. It can alleviate CIRI and reduce brain injury through inhibiting inflammation, oxidation, and apoptosis, protecting blood-brain barrier, and activating mitophagy. However, little is known about the specific mechanism and molecular targets. In view of the low bioavailability and poor solubility of quercetin, researchers have developed a variety of delivery systems to facilitate the dispersion of quercetin, improve chemical stability, and increase clinical application. Furthermore, researchers have tested the long-term safety of quercetin and confirmed that low-dose quercetin has good safety. By reviewing the relevant studies in recent years, we summarized the targets, mechanism, delivery, and safety of quercetin in the treatment of CIRI, aiming to provide a theoretical basis for the further development and application of quercetin.
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The fate of mesenchymal stem cells (MSCs) is regulated by biological, physical and chemical signals. Developments in biotechnology and materials science promoted the occurrence of bioactive materials which can provide physical and chemical signals for MSCs to regulate their fate. In order to design and synthesize materials that can precisely regulate the fate of MSCs, the relationship between the properties of materials and the fate of mesenchymal stem cells need to be clarified, in which the detection of the fate of mesenchymal stem cells plays an important role. In the past 30 years, a series of detection technologies have been developed to detect the fate of MSCs regulated by bioactive materials, among which high-throughput technology has shown great advantages due to its ability to detect large amounts of data at one time. In this review, the latest research progresses of detecting the fate of MSCs regulated by bone bioactive materials (BBMs) are systematically reviewed from traditional technology to high-throughput technology which is emphasized especially. Moreover, current problems and the future development direction of detection technologies of the MSCs fate regulated by BBMs are prospected. The aim of this review is to provide a detection technical framework for researchers to establish the relationship between the properties of BMMs and the fate of MSCs, so as to help researchers to design and synthesize BBMs better which can precisely regulate the fate of MSCs.
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Yuhua91 is a new peanut variety with high oleic acid content bred by Qingdao Agricultural University. The crossing was conducted with Luhua11 as female parent and with Kainong1715, an F435-type variety with high oleic acid content as male parent. The real F1 hybrids were screened by sequencing on PCR amplification products, and those homozygotes with bb genotype in F2 populations were screened by the same sequencing method as above. The content of oleic and linoleic acid was measured on the kernels harvested from F2 single plants by near infrared ray method, and those kernels whose content of oleic was above 80%, oleic and linoleic acid ratio was above 10.0 were obtained and planted into a row, with pedigree method for subsequent selection breeding. Yuhua91 has some characters of small pod, light and obvious pod texture, 148.06 g per 100 pods, 63.31 g per 100 kernels, 75.15% shelling percentage, long elliptic seed kernel, pink seed coat, without crack, white endotesta. Its content of protein, oil, oleic acid, linoleic acid and palmitic acid was 26.57%, 52.72%, 80.40%, 2.50% and 5.57% respectively. Yuhua91 has other characters of strong seedlings, compact pod areas, and moderate resistance to leaf spot disease and bacterial wilt. Average pod yield is 215.79 kg per Mu, 15.27% higher than the control variety Huayu20. Average seed kernels yield is 157.33 kg per Mu, 21.64% higher than the control variety Huayu20. Yuhua 91 has been registered on department of agriculture in 2018, and the registration No. is GPD peanut (2018) 370210, fit for growing in Shandong Province.
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Arachis , Ácido Oléico , Fitomejoramiento , SemillasRESUMEN
Leaf water potential of peanut subjected to drought stress is positively related to the oil content of peanut kernels. The aim of this study was to directly screen the high oil mutants of peanut and create the new peanut varieties using hydroxyproline as water potential regulator. In vitro mutagenesis was carried out with the embryonic leaflets of peanut variety Huayu 20 as explants and pingyangmycin as a mutagen added into the somatic embryo formation medium. The formed somatic embryos were successively transferred to somatic embryo germination and selection medium containing 6 mmol/L hydroxyproline (at -2.079 MPa water potential ) to induce regeneration and directionally screen high oil content mutants. After that, these plantlets were grafted and transplanted to the experimental field and 132 high oil mutants with oil content over 55% were obtained from the offspring of regenerated plants. Finally, among them, the oil contents of 27 lines were higher than 58% and of 2 lines were higher than 60%. A new peanut variety Yuhua 9 with high yield and oil content was bred from the regenerated plant progenies combining the pedigree breeding method. The yield was 14.0% higher than that of the control cultivar in the testing new peanut varieties of Liaoning province, and also it has passed the national registration of non-major crop varieties. Yuhua 9 with an oil content of 61.05%, which was 11.55 percentage points higher than that of the parent Huayu 20, was the peanut cultivar with the highest oil content in the world. The result showed that it was an effective way for directional breeding of high oil peanut varieties by means of the three-step technique including in vitro mutagenesis, directional screening by reducing water potential in medium and pedigree selection of regenerated plant progenies.
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Arachis , Sequías , Germinación , Mutagénesis , FitomejoramientoRESUMEN
Objective To explore the therapeutic effect of different doses of botulinum toxin A injections on bromhidrosis.Methods A total of 200 cases were divided into mild-to-moderate group (N=100) and severe group (N=100) based on the grade of bromhidrosis,and each group was further divided into two groups:low dose group (50 cases) were treated by botulinum toxin A injections (100 U) and high dose group (50 cases) were treated with 200 U for bilateral axillary.The total effective rate and recurrence rate in both groups were compared.Results In the mild to moderate group,after treatment for 3 months,the total effective rate of both groups had no statistical difference (P> 0.05),and the same with recurrence rate in 6 months follow-up (P>0.05).In the severe group,after treatment for 3 months,the total effective rate of the high dose group (82%) was significantly higher than that of the low dose group (64%),with statistical significance (x2 =4.110,P<0.05).After 6 months follow-up,recurrence rate in the high dose group (22%) was significantly lower than that of the low dose group (46%),with statistical significance (x2 =6.417,P < 0.05).Conclusions A suitable dose of botulinum toxin A can be selected based on the severity of bromhidrosis,which is a individualized therapy for cost savings and might have potential benefits for patients with osmidrosis.
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AIM:To establish and characterize the patient-derived esophageal squamous-cell carcinoma xeno-graft (PDECX) in mice.METHODS:The samples of human esophageal cancer were grafted into severe combined immu-nodeficient ( SCID) mice.The xenografts were transferred to SCID mice when the first passage of xenografts grew up .The growth of tumors in the first, second and third passages was observed .HE staining was performed.The expression of CK5/6, p63 and p40 in the patient samples , and the first and third passages of the xenografts were detected by immunohisto-chemical analysis.The expression of mTOR, p-mTOR, p70S6K, p-p70S6K, Akt1, p-Akt (Ser473), Erk1/2 and p-Erk1/2 were determined by Western blot .RESULTS:The PDECX was successfully established .The positive expression of CK5/6, p63 and p40 in the xenografts was consistent with that in the patients ’ samples.The levels of phosphorylated and total proteins of proliferation-related signaling pathways were different in the xenografts from different patients .CONCLU-SION:The PDECX model adequately reflects the tumal heterogeneity that is observed in the patients .
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[ ABSTRACT] AIM:To investigate the effect of atorvastatin on the development of heart failure after myocardial infarction and the association with sodium-calcium exchanger (NCX) expression.METHODS:The model of heart failure was established by ligation of the anterior descending coronary artery for 8 weeks.The rats were randomly divided into con-trol group, heart failure group, and atorvastatin group.Either atorvastatin (10 mg· kg-1· d-1) or vehicle was orally ad-ministered to the rats on the next day after the surgery .The left ventricular function and NCX expression were analyzed 8 weeks after ligation .Neonatal rat cardiomyocytes were cultured to investigate the effect of atorvastatin on the changes of cal -cium concentration induced by hypoxemia .RESULTS: A decrease in left ventricular diastolic dimension , an increase in left ventricular fractional shortening , and reductions of BNP level and NCX expression were observed in atorvastatin group . The hypoxemia-induced calcium overload in cultured cardiomyocytes was inhibited by atorvastatin , and it was inhibited by the inhibitor of NCX .CONCLUSION:Atorvastatin treatment improves cardiac function , which may be related to the ex-pression and function of sodium calcium exchanger in heart failure .
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Objective:To select suitable chemotherapy for cervical cancer patients by ATP-tumor chemosensitivity assay. Methods:Seventy-two hospitalized patients with cervical cancer between July 2007 and October 2009 were enrolled. The patients were randomly divided into a trial group (n=35) and a control group(n=37). ATP-TCA was used to detect the sensitivity of 35 samples of cervical cancer in the trial group to 6 combined chemotherapy regimens. The chemotherapy regimen in the trial group was confirmed by the results of susceptibility testing and that in the control group was confirmed by clinical experience. One-year recurrence rate and 3-year survival rate of two groups were compared after 3 year follow-up. Results:ATP-TCA was measured in 32 of the 35 patients in the trial group. The sensitive patients for paclitaxel+carboplatin, paclitaxel+oxaliplatin, bleomycin+ifosfamide+cisplatin, bleomycin+vincristine+cisplatin, fluorouracil+cisplatin, and gemcitabine+cisplatin were 20, 18, 17, 18, 17, and 21, respectively. There was no significant difference in the 1-year recurrence between the two groups (P>0.05), while the 3-year survivors in the trial group were more than those in the control group (P Conclusion:ATP-TCA method is good for patients with cervical cancer because it is sensitive, effective, and individualized.
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Objective To study the foxml gene and its protective effect on the lung tissue of rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), and to observe the dexamethason' s (DEX) impacts on foxml gene and the prognosis of ALI. Method Seventy-two healthy mice were randomly(random number) divid-ed into three groups: control group (A group, n = 24), model group (B group, n = 24) and DEX treatment group (C group, n = 24). The observing intervals were respectively set in 24 h, 48 h and 72 hours. At each ob-serving interval, the foxml protein in lung tissue of mice was detected by using immunohistochemistry (IHC), and the expression of foxml gene in lung tissue was detected by using RT-PCR, as well as to observe the pathological changes in lung tissue. Results Comparisons were made between paired groups at 24 h,48 h and 72 h intervals in which the expression of foxml mRNA and the level of foxml protein in lung tissue of mice in C group were signifi-cantly higher than those in B group (P < 0.05), and those in B group were significantly higher than those in A group (P < 0.05). The expression of foxml mRNA and the level of foxml protein in lung tissue of mice in B group at 48 h interval were significantly higher than those both at intervals of 72 h and 24 h (P < 0.05), and the those at 72 interval were significantly higher than those at 24 h interval (P < 0.05). Compared with B group, the pathologi-cal changes in lung tissue of mice in C group were lessened. Conclusions In both model group and dexamethasone treatment group, the expression of foxml mRNA and the level of foxml protein in lung tissue of mice are increased significantly. Dexamethasone lessens the injury of both vascular endothelial cells and alveolar epithelial ceils of lung tissue, and it also significantly increases the expression of foxml mRNA and the level of foxml protein.
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Objective To characterise the alterations of serum autoantibodies for cyclinB1,p62,Koc-IMP1 and survivin in the subjects with esophgeal and gastric cardia carcinoma and precancerous lesion and their expres-sions in the esophageal and gastric cardia cancer tissue.Methods Enzyme-linked immunoassay and tumor-associated antigen mini-array (consisting of five full-length recombinant proteins,including eyefinB1-p62-Koc,IMP1 and Survivin)were applied to determine the serum level of the autoantibodies of these antigens on 376 subjects with e-sephageal and gastric cardia carcinoma and precancerous lesions.At the same time,the expression of these antigens was detected by immunohistochemical method(ABC)on 13 patients with esophageal cancer and 16 with gastric car-dia cancer.Results All of the 5 antigens determined,the linear correlation Was observed for the detection frequency of cyclinB1,IMPI and p62 in esophageal carcinogenesis,and for p62 in gastric cardia multi-stage progression from normal to precancerous and cancerous lesions(P<0.05).The detection rale with single positive antoantibody im-munoreactivity for both esophageal and gastric cardia cancers were low.However.the positive detection mte for both esophageal and gastric cardia cancer increased apparently when the multiple positive markers were combined together for analysis,which increased tO 3~5 and 3~4 folds respectively.Furthermore,the difference in autoantibody immu-noreactive rate was significant with the lesion progressed from mild tO severe precancerous lesions and to cancer both in esophageal and gastric cardia cancers(P<0.05).The positive immunoreactions of the 5 antigens were detected in cancer tissues.The positive immunostaining rates for cyclinB1,Koc,IMP1 and Survivin both in esophageal and gastric cardia cancers were higher compared to their serllin positive rate of autoantibodies I P<0.05).Of the pa-tients with positive immunostaining in the two cancer tissues,the autoantibodies in the serum for the corresponding antigens could be detected in the same patient.Conclusion The production of the tumor-associated autoantibodies is related tO antigens.The screening rate through serum tumor-associated antigen mini-array for the patients with e-sophageal and gastric cardia carcinoma and precancerous lesions has been increased apparently with combined analy-sis of multiple autoantibodies than with single one.